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Microtrauma in the lumbar spine: a cause of low back pain.

Excessive mechanical stress on the intervertebral disc may be one of the causes of low back pain. Most studies testing this thesis, however, have been based on quantification of the mechanical response of functional units at failure. Typically, radiography is used to demonstrate trauma to the vertebral body at the failure load. The description of failure and radiographic demonstration of damage are meaningful in specifying the tolerance limits of the structure. It is important, however, to understand the sequence underlying the initiation of injury, which may occur at subfailure physiological loads. In this study, we identified the initiation of injury to the lumbar spine by subjecting functional units to axial compressive loads using the mechanical response as a basis. Because conventional radiography failed to detect trauma at this level, advanced sectioning techniques were used. The initiation of injury (microtrauma) is defined as the point on the load-deflection curve where the structure exhibits a decreasing level of resistance for the first time before reaching its ultimate load-carrying capacity. The load deflection curve on this basis was classified into the ambient or preload phase, physiological loading phase, traumatic phase, and post-traumatic phase. Structures loaded to the end of the physiological loading phase did not exhibit any yielding or microtrauma. Injury in the form of microfractures of the endplate not detected on radiography, however, was observed under cryomicrotomy for structures loaded into the traumatic loading phase.

Adult↗

Intravertebral pressure changes caused by spinal microtrauma.

Clinical studies indicate variations in intravertebral pressures in patients with and without low back pain. It is known that not all patients with back pain have abnormal lumbar radiographs and, furthermore, microfractures of the endplate may be one of the causes in the origin of low back pain. Consequently, this study was conducted to determine the interrelationship between microtrauma and intraosseous pressures in the lumbar spine. Miniature pressure transducers were inserted into the vertebral bodies and spinous processes of human cadaver spinal units. Radio-opaque medium was injected into the nucleus to fluoroscopically monitor the movement of the fluid from the disc as the preparation was loaded up to the initiation of microtrauma (before reaching the ultimate load-carrying capacity). The onset of injury was evidenced by the microfracture of one of the two endplates and impregnation of the contrast medium into the spongiosa. After relaxation, another cycle of loading was applied by limiting the deflections to the maximum compression sustained under the intact configuration. The load, stiffness, and energy-absorbing capacities were lower (P < 0.05) for the injured specimen compared with the intact configuration. The intraosseous pressures were higher (P < 0.05) in the vertebral body and the spinous process of the vertebra where the endplate exhibited microtrauma in the injured cycle compared with the intact cycle. In contrast, the intraosseous pressures in the vertebral body and the spinous process at the level where the endplate remained intact were not significantly different between the two cycles of loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Non-invasive imaging of blood cell concentration and blood distribution in zebrafish Danio rerio incubated in hypoxic conditions in vivo.

This is the first study to use a combination of digital imaging techniques and vital video microscopy to study hypoxia-induced changes in blood cell concentration, angiogenesis and blood redistribution in entire animals. Zebrafish Danio rerio, which are known to be independent of convective oxygen transport until about 2 weeks post-fertilization, were raised under chronic hypoxia (P(O(2))=8.7 kPa) starting at 1 day after fertilization (d.p.f.) until 15 d.p.f. In control animals, the concentration of red cells (i.e. the number of red cells per nl blood) remained constant until 7 d.p.f., and than decreased by approximately 70% until 15 d.p.f. In hypoxic animals, however, the concentration of red cells remained significantly elevated compared to control animals at 12 and 15 d.p.f. Assuming that the hemoglobin content of the red cells is similar, hypoxic animals have a higher oxygen carrying capacity in their blood. Red cell distribution within the various parts of the circulatory system, taken as an indicator for blood distribution, revealed a significant modification in the number of blood cells perfusing the organs in hypoxic animals. At 12 d.p.f., gut perfusion was reduced by almost 50% in hypoxic animals, while perfusion of the segmental muscle tissue was increased to 350% of control values. No significant changes in brain perfusion were observed under these conditions. At 15 d.p.f., the reduction in gut perfusion was abolished, although muscle perfusion was still significantly elevated. At this time, growth of hypoxic animals was less compared to control animals, revealing that hypoxia had become deleterious for further development. The vascular bed of various organs was not obviously different in hypoxic animals compared to normoxic animals.

Analysis of Variance↗

Acclimation to hypothermic incubation in developing chicken embryos (Gallus domesticus): II. Hematology and blood O2 transport.

Hypothermic incubation reduces the ability of the late-stage chicken embryo to mount endothermic heat production. This study investigates whether blood O(2) transport is similarly limited by cooler incubation temperatures. Two populations of chicken embryos were incubated at 38 degrees C and 35 degrees C. At Hamilton-Hamburger (HH) developmental stage 41-42, hypothermic incubation had no significant effect on hematocrit ( approximately 26%) or [Hb] (7 g%). However, in the final stages of incubation (stage 43-44), hypothermic incubation reduced hematocrit from approximately 31% at 38 degrees C to approximately 27.5% at 35 degrees C. Hypothermic incubation similarly caused a reduced [Hb] from 8.5 g% (38 degrees C) to 6.25 g% (35 degrees C), indicating a reduction in blood O(2)-carrying capacity in embryos. Incubation temperature had a strong effect on blood-O(2) affinity in late development (stage 43-44), with P(50) at 38 degrees C falling significantly from approximately 6 kPa in 38 degrees C embryos to approximately 4 kPa in 35 degrees C embryos. P(O(2)) values in chorioallantoic arterial blood at HH 41-42 were 4.3 kPa at pH 7.46 (38 degrees C) and 3.4 kPa at pH 7.39 (35 degrees C). In chorioallantoic venous blood these values were 9.1 kPa at pH 7.34 (38 degrees C) and 8.1 kPa at pH 7.42 (35 degrees C). With further development to HH 43-44, chorioallantoic arterial blood oxygenation fell to 2.4 kPa at pH 7.54 (38 degrees C) and 2.8 kPa at pH 7.52 (35 degrees C). Similarly, P(O(2)) in chorioallantoic venous blood fell slightly to 7.7 kPa at pH 7.42 (38 degrees C) and 7.4 kPa at pH 7.48 (35 degrees C). Collectively, these data reveal that beyond HH 41-42, 35 degrees C embryos experience retarded hematological development, and the findings that support the observed delayed metabolic response to acute temperature changes.

2,3-Diphosphoglycerate↗

Cardiorespiratory modifications, and limitations, in post-smolt growth hormone transgenic Atlantic salmon Salmo salar.

In recent years, there has been a great deal of interest in how growth hormone (GH) transgenesis affects fish physiology. However, the results of these studies are often difficult to interpret because the transgenic and non-transgenic fish had very different environmental/rearing histories. This study used a stable line of size-matched GH Atlantic salmon (Salmo salar) that were reared in a shared tank with controls (at 10 degrees C, for approximately 9 months) to perform a comprehensive examination of the cardiorespiratory physiology of GH transgenic salmon, and serves as a novel test of the theory of symmorphosis. The GH transgenic salmon had a 3.6x faster growth rate, and 21 and 25% higher values for mass-specific routine and standard oxygen consumption (M(O(2))), respectively. However, there was no concurrent increase in their maximum M(O(2)), which resulted in them having an 18% lower metabolic scope and a 9% reduction in critical swimming speed. This decreased metabolic capacity/performance was surprising given that the transgenics had a 29% larger heart with an 18% greater mass-specific maximum in situ cardiac output, a 14% greater post-stress blood haemoglobin concentration, 5-10% higher red muscle and heart aerobic enzyme (citrate synthase or cytochrome oxidase) activities, and twofold higher resting and 1.7x higher post-stress, catecholamine levels. However, gill surface area was the only cardiorespiratory parameter that was not enhanced, and our data suggest that gill oxygen transfer may have been limiting. Overall, this research: (1) shows that there are significant metabolic costs associated with GH transgenesis in this line of Atlantic salmon; (2) provides the first direct evidence that cardiac function is enhanced by GH transgenesis; (3) shows that a universal upregulation of post-smolt (adult) GH transgenic salmon cardiorespiratory physiology, as suggested by symmorphosis, does not occur; and (4) supports the idea that whereas differences in arterial oxygen transport (i.e. cardiac output and blood oxygen carrying capacity) are important determinants of inter-specific differences in aerobicity, diffusion-limited processes must be enhanced to achieve substantial intra-specific improvements in metabolic and swimming performance.

Animals↗

Delayed development and lifespan extension as features of metabolic lifestyle alteration in C. elegans under dietary restriction.

Studies of the model organism Caenorhabditis elegans have almost exclusively utilized growth on a bacterial diet. Such culturing presents a challenge to automation of experimentation and introduces bacterial metabolism as a secondary concern in drug and environmental toxicology studies. Axenic cultivation of C. elegans can avoid these problems, yet past work suggests that axenic growth is unhealthy for C. elegans. Here we employ a chemically defined liquid medium to culture C. elegans and find development slows, fecundity declines, lifespan increases, lipid and protein stores decrease, and gene expression changes relative to that on a bacterial diet. These changes do not appear to be random pathologies associated with malnutrition, as there are no developmental delays associated with starvation, such as L1 or dauer diapause. Additionally, development and reproductive period are fixed percentages of lifespan regardless of diet, suggesting that these alterations are adaptive. We propose that C. elegans can exist as a healthy animal with at least two distinct adult life histories. One life history maximizes the intrinsic rate of population increase, the other maximizes the efficiency of exploitation of the carrying capacity of the environment. Microarray analysis reveals increased transcript levels of daf-16 and downstream targets and past experiments demonstrate that DAF-16 (FOXO) acting on downstream targets can influence all of the phenotypes we see altered in maintenance medium. Thus, life history alteration in response to diet may be modulated by DAF-16. Our observations introduce a powerful system for automation of experimentation on healthy C. elegans and for systematic analysis of the profound impact of diet on animal physiology.

Animals↗

OXYGEN TRANSPORT IN MARINE GREEN TURTLE (CHELONIA MYDAS) HATCHLINGS: BLOOD VISCOSITY AND CONTROL OF HEMOGLOBIN OXYGEN-AFFINITY

Erythrocytes from green turtle hatchlings contain a single embryonic component, unlike those from other cleidoic eggs, in which adult hemoglobin (Hb) constitutes a significant fraction of total Hb at hatching. The functional properties of the isolated and purified green turtle hatchling Hb that distinguish it from adult Hb are a high affinity for oxygen and marked sensitivity to organic phosphate modulators. Hatchling erythrocytes also contain higher concentrations of ATP and 2,3-diphosphoglyceric acid, but their oxygen affinity is indistinguishable from that of adult erythrocytes. Hatchling erythrocyte mean cell volume is approximately half of the adult value, but hematocrit, blood hemoglobin concentration and blood viscosity of hatchlings and adults are similar. Oxygen-carrying capacity in green turtles, unlike that of other diving vertebrates, corresponds with a theoretically derived optimum. The possibility of allosteric control of Hb oxygen-binding in hatchlings may relate not to the challenge of exercise during the dispersal phase but to conditions in the late embryo in the nest.

Journal Article↗

EXERCISE IN THE TERRESTRIAL CHRISTMAS ISLAND RED CRAB GECARCOIDEA NATALIS - BLOOD GAS TRANSPORT

The respiratory and circulatory physiology of the terrestrial Christmas Island red crab Gecarcoidea natalis was investigated with respect to exercise in the context of its annual breeding migration. Red crabs were allowed to walk for predetermined periods of up to 45 min. During this exercise period, blood gas measurements were made on venous, pulmonary and arterial samples to assess the function of the lungs in gas exchange and the performance of the circulatory system in gas transport and to determine the role and importance of the haemocyanin. The lungs of G. natalis were very efficient at O2 uptake, pulmonary blood being 80&shy;90 % saturated throughout the 45 min exercise period. The maximum O2-carrying capacity was 1.1 mmol l-1, and haemocyanin (Hc) delivered 86 % of oxygen in resting crabs and 97 % during exercise. Oxygen delivery to the tissues was diffusion-limited during exercise. Indirect evidence, from the changes in haemolymph pH during transit through the lungs, suggested that the lung is the site of CO2 excretion. The Bohr shift was high at high pH (pH 7.8&shy;7.5, phi=-1.23) but decreased at low pH (pH 7.1&shy;6.8, phi=-0.48). The decreased Hc affinity for O2 during the exercise period facilitated O2 delivery to the tissues without impairing O2 loading at the lungs. The decrease in pH was sufficient to explain the change of affinity of Hc for O2 during the exercise period. The marked acidosis (0.8 pH unit decrease) was largely metabolic in origin, especially during sustained locomotion, but less than could be predicted from concomitant lactate production.

Journal Article↗

The interaction of pulmonary ventilation and the right-left shunt on arterial oxygen levels.

In adult mammals, arterial blood gases closely reflect lung gas composition, and arterial blood gases can, therefore, be effectively regulated through changes in ventilation. This is not the case among most ectothermic vertebrates, where the systemic and pulmonary circulations are not completely separated, resulting in central vascular shunts. In the presence of a right-to-left shunt (R-L shunt), the O2 levels (PO2 and haemoglobin O2-saturation) of systemic arterial blood are depressed relative to those of the blood returning from the lungs. Arterial blood gas composition is, accordingly, not determined only by ventilation, but also by the magnitude of admixture as well as the blood gas composition of systemic venous blood. Changes in the central shunt patterns, therefore, represent an alternative mechanism by which to control arterial blood gas levels. The primary aim of this report is to evaluate the relative importance of the R-L shunt and ventilation in determining arterial blood gas levels. Using standard equations for gas exchange and the two-compartment model, we predicted arterial O2 levels at physiologically relevant levels of ventilation, R-L shunt and blood flows. The analyses show that the effects of changing ventilation and the size of the R-L shunt on arterial O2 levels vary with parameters such as the rate of O2 uptake, the blood O2-carrying capacity and the level of hypoxia. The relative importance of ventilation and the R-L shunt in determining arterial PO2 values is largely explained by the sigmoidal shape of the O2 dissociation curve. Thus, if lung PO2 is high relative to blood O2 affinity, a large change in ventilation may have little effect on pulmonary venous O2 content, although PO2 may have changed considerably. If an R-L shunt is taking place, this, in turn, implies that arterial O2 content is affected only marginally, with a correspondingly small effect on PO2. These predictions are discussed in the light of the limited existing experimental data on cardiac shunts in lower vertebrates; we propose that, in future experiments, the measurement of both ventilatory and cardiovascular parameters must be combined if we aim to understand the regulation of arterial blood gas levels in lower vertebrates.

Animals↗

Oxygen transport and cardiovascular responses to exercise in the yellowfin tuna Thunnus albacares.

Yellowfin tuna Thunnus albacares (1400-2175 g) instrumented with electrocardiogram electrodes and pre- and post-branchial catheters were subjected to incremental swimming velocity tests. Increasing velocity, from a minimal speed of 1.0 FLs-1, where FL is fork length, resulted in a 1.4-fold increase in heart rate (from 61.4 to 84.6 beats min-1), an elevated ventral-aortic blood pressure (from 10.8 to 12.2 kPa) and a decreased systemic vascular resistance. Relative branchial vascular resistance at minimal speed ranged from 24.4 to 40.0% of total vascular resistance and tended to increase with velocity. Yellowfin blood has a high oxygen-carrying capacity (16-18 ml O2 dl-1), and a low in vivo oxygen affinity (P50 = 5.3 kPa). Exercise caused a rise in arterial saturation (from 74 to 88%) and a decline in venous saturation (from 48 to 44%), resulting in a 1.3-fold increase in tissue oxygen extraction from the blood (arterial-venous oxygen content difference). Whereas arterial oxygen partial pressure (PO2) tended to increase with exercise, venous PO2 remained unchanged (approximately 5.3 kPa). The observed decrease in venous oxygen content was brought about by a lowered blood pH (from 7.80 to 7.76) and a large Bohr shift. Cardiac output and the increased blood oxygen extraction are estimated to have contributed nearly equally to the increased oxygen consumption during exercise. The large venous oxygen reserve still available to yellowfin tuna at maximal prolonged velocities suggests that the maximal oxygen delivery potential of the cardiovascular system in this species is not fully utilized during aerobic swimming. This reserve may serve other aerobic metabolic processes in addition to continuous swimming.

Animals↗

Flight performance during hunting excursions in Eleonora's falcon Falco eleonorae.

Among birds, falcons are high-performance flyers, in many cases adapted for aerial hunting and hence suitable targets for investigating limits to flight performance. Using an optical range finder, we measured flight tracks of Eleonora's falcon (Falco eleonorae), a species breeding in the Mediterranean region and specialised for hunting autumn passage bird migrants, when commuting between their nesting colony and offshore hunting areas (straight transportation flight) and when searching for prey (transecting and searching flight). Airspeed during searching flight was significantly slower than during straight transportation and transecting flight, but there was no significant difference in airspeed between the latter two flight modes. Straight transportation flight was significantly faster than predicted minimum power speed. Also, during straight transportation flight, the falcons responded to head- and tailwinds by increasing their airspeed when flying into the wind. However, they did not show any significant airspeed adjustments with respect to the angle between the track and the heading, as would be expected in birds trying to maintain a constant track direction. Mean sustainable climb rate (during (greater than or equal to) 240 s) was 1.4+/-0.31 m s-1 (mean +/- s.d., N=13), which is rather a high rate for a bird the size of an Eleonora's falcon. The climb rate was used to calculate maximum load-carrying capacity and maximum sustained horizontal flapping flight speed. The mean wingbeat frequency during powered climbing flight was 4.68 Hz, which was used to estimate the mass-specific muscle work. When falcons were leaving the colony for offshore hunting, they gained altitude by slope-soaring when there was an onshore wind. We formulated a simple criterion for the required gliding-flight rate of climb during an initial slope-soaring episode when minimizing the energy cost of reaching a certain altitude far out over the sea (which is where the prey is to be found). This climb rate was 0.36 m s-1, and our observations indicated that the falcons experienced climb rates above this value when soaring in slope-lift.

Animals↗

Effect of brood size manipulation on offspring physiology: an experiment with passerine birds.

The environment experienced during ontogeny has a significant impact on the physiological condition of offspring. This, in turn, forecasts survival probabilities and future reproductive potential. Despite the prominent role that the concept of condition plays in evolutionary studies, the physiological and biochemical characters that define it remain relatively unexplored. In this study, we quantified the impact of brood size manipulations on the physiology and biochemistry of nestling tree swallows (Tachycineta bicolor) shortly before they fledged. Over two breeding seasons, we either increased or decreased the number of individuals in a brood by a single nestling. Every 2-4 days, we determined the resting rate of oxygen consumption [V(O(2))] of individuals in each brood. Growth was followed until 16 days of age, at which time, to look for potential trade-offs in energy allocation, we measured total lipid mass, skeletal muscle and organ mass, indices of blood oxygen-carrying capacity and the activities of key metabolic enzymes in various tissues. Surprisingly, there was a minimal response of most characters to brood manipulation, suggesting that physiological and biochemical development is relatively invariant except perhaps under extreme conditions. Individuals reared in artificially enlarged broods, however, had a significantly lower body mass, body-size-adjusted [V(O(2))], gizzard mass and total lipid mass. These individuals also had decreased activity of cardiac 3-hydroxyacyl CoA dehydrogenase, suggesting a decreased capacity for oxidation of fatty acids. How these characters affect survival or the future adult phenotype remains unknown.

3-Hydroxyacyl CoA Dehydrogenases↗

Oxygen-sensitive membrane transporters in vertebrate red cells.

Oxygen is essential for all higher forms of animal life. It is required for oxidative phosphorylation, which forms the bulk of the energy supply of most animals. In many vertebrates, transport of O(2) from respiratory to other tissues, and of CO(2) in the opposite direction, involves red cells. These are highly specialised, adapted for their respiratory function. Intracellular haemoglobin, carbonic anhydrase and the membrane anion exchanger (AE1) increase the effective O(2)- and CO(2)-carrying capacity of red cells by approximately 100-fold. O(2) also has a pathological role. It is a very reactive species chemically, and oxidation, free radical generation and peroxide formation can be major hazards. Cells that come into contact with potentially damaging levels of O(2) have a variety of systems to protect them against oxidative damage. Those in red cells include catalase, superoxide dismutase and glutathione. In this review, we focus on a third role of O(2), as a regulator of membrane transport systems, a role with important consequences for the homeostasis of the red cell and also the organism as a whole. We show that regulation of red cell transporters by O(2) is widespread throughout the vertebrate kingdom. The effect of O(2) is selective but involves a wide range of transporters, including inorganic and organic systems, and both electroneutral and conductive pathways. Finally, we discuss what is known about the mechanism of the O(2) effect and comment on its physiological and pathological roles.

Animals↗

On the respiration of Torpedo marmorata.

1. The oxygen consumption of resting Torpedo marmorata was measured using three different methods. The results indicate that this species has a much lower oxygen consumption than other elasmobranchs of comparable size. 2. The gills are ventilated by a mechanism similar to that of other rays, but a relatively small spiracular opening seems to be associated with a more important role of the oro-branchial pump. During hypoxia there is a marked increase in both frequency and amplitude of the ventilatory movements. 3. The frequency of the heart beat is low and shows little change during hypoxia, except under extreme conditions when bradycardia occurs. 4. In some individuals, coupling between cardiac and ventilatory pumps is relatively low but seems to increase at lower ventilatory frequencies and when the ratio between the ventilatory and cardiac frequencies is a whole number. 5. Extreme hypoxia can be withstood for many hours but eventually the ventilatory rhythm ceases; it does not recommence immediately following a rise in ambient oxygen tension. 6. The blood has a low oxygen-carrying capacity and a high affinity. 7. The surface area of the gills is smaller than that of other species that have been investigated, but the quantity of oxygen transferred/unit surface area is similar to that known for other species. 8. It is concluded that Torpedo is a sluggish fish adapted to conditions of low oxygen, but the conditions under which this occurs remain to be determined.

Animals↗

Pathophysiology of the atherosclerotic rabbit.

The pathophysiology and histopathology caused by feeding rabbits a diet containing 2% cholesterol is described. Cholesterol deposition was seen in almost all organs after 15 weeks on the diet. Lesions were seen as early as 7 weeks in the aorta and pulmonary vessels and by 11 weeks in the small intramyocardial arteries and arterioles. Evidence of myocardial ischemia could be elicited by stressing the heart by electrical pacing at rapid rates or by administration of pharmacological agents which increased oxygen consumption (isoproterenol) or decreased oxygen supply (ergonovine). Susceptibility to such stress was increased by isovolumic hemodilution which decreased the oxygen-carrying capacity of the blood. Myocardial fibrosis and infarction were evident by 15 weeks on the diet and cardiac reserve was depleted by 25 weeks as evidenced by the presence of ascites in all animals examined. The preliminary results reported here suggest that further evaluation of the atherosclerotic rabbit as a cardiac toxicity model is warranted.

Animals↗

All that glitters is not iron (deficiency): revisiting the question of why anemic individuals are anemic.

Three recent surveys from Kenya, the Ivory Coast, and East Java emphasize that anemia is a complex and multifaceted public health problem. A thorough understanding of iron metabolism and its disturbance is central to resolving the problem of anemia but requires intricate analysis. To maximize oxygen-carrying capacity and optimize human function, one must combine issues of sociology, economics, and general health with multiple micronutrient interventions.

Anemia, Iron-Deficiency↗

Sampling-theory approach to eigenwavefronts of imaging systems.

We present a direct method based on the sampling theorem for computing eigenwavefronts associated with linear space-invariant imaging systems (including aberrated imaging systems). A potential application of the eigenwavefronts to inverse problems in imaging is discussed. A noise-dependent measure for the information-carrying capacity of an imaging system is also proposed.

Journal Article↗

Myocardial oxygen supply and demand.

The supply of oxygen to the myocardium is determined by coronary blood flow and oxygen carrying capacity. Coronary blood flow is a dynamic process modulated via multiple parameters. Cardiac metabolism is also affected by several factors. Under normal physiologic conditions, the demand is easily met by the supply of oxygen. In fact, there is a significant reserve on the supply side. Under certain pathologic states such as coronary artery disease, the supply of oxygen may be exhausted and an imbalance between supply and demand occurs which is translated into ischemia. The area of myocardium most susceptible to ischemia is the subendocardium due to mechanical and metabolic forces. In therapy of coronary artery disease, attention should be directed to directional changes in factors influencing supply and demand to improve blood flow to the most susceptible area.

Coronary Circulation↗