Relationship between capillaries, mitochondria and maximum power of the heart: a meta-study from shrew to elephant.

This meta-study uses phylogenetic scaling models across more than 30 species, spanning five orders of magnitude in body mass, to show that cardiac capillary numerical density and mitochondrial volume density decrease with body mass raised to the -0.07 ± 0.03 and -0.04 ± 0.01 exponents, respectively. Thus, while an average 10 g mammal has a cardiac capillary density of approximately 4150 mm-2 and a mitochondrial density of 33%, a 1 t mammal has considerably lower corresponding values of 1850 mm-2 and 21%. These similar scaling trajectories suggest quantitative matching for the primary oxygen supply and oxygen consuming structures of the heart, supporting economic design at the cellular level of the oxygen cascade in this aerobic organ. These scaling trajectories are nonetheless somewhat shallower than the exponent of -0.11 calculated for the maximum external mechanical power of the cardiac tissue, under conditions of heavy exercise, when oxygen flow between capillaries and mitochondria is probably fully exploited. This mismatch, if substantiated, implies a declining external mechanical efficiency of the heart with increasing body mass, whereby larger individuals put more energy in but get less energy out, a scenario with implications for cardiovascular design, aerobic capacity and limits of body size.

Morphology of the nutrient artery and its foramen in relation to femoral bone perfusion rates of laying and non-laying hens.

If arteries penetrate bones through foramina, regional artery blood flow rates can be estimated from the foramen sizes. Femoral bone blood flow rates estimated from nutrient foramen sizes were previously not absolute, but only a relative blood flow index (Qi ), because the size relationship between the foramen and the occupying artery was unknown. The current study used vascular contrast and micro-computerized tomographic scanning to investigate femoral nutrient foramen and nutrient artery sizes in three groups of sub-adult chickens (non-laying hens, laying hens, and roosters) of similar ages. The results indicate that the cross-sectional area of the nutrient artery lumen occupies approximately 20.2 ± 4.1% of the foramen for femora with only one foramen. Artery lumen size is significantly correlated with foramen size. Vascular contrast imaging is capable of estimating blood flow rates through nutrient arteries, as blood flow rates estimated from artery lumen casts are similar to blood flow rates measured by infusion of fluorescent-labeled microspheres. Laying hens tend to have higher nutrient artery perfusion rates than non-laying hens, probably due to extra oxygen and calcium requirements for eggshell production, although the calculated blood flow difference was not statistically significant. Histological embedding and sectioning along with vascular contrast imaging reveal variable nutrient foramen morphology and nutrient artery location among femora with more than one nutrient foramen.

Whole-body endothermy: ancient, homologous and widespread among the ancestors of mammals, birds and crocodylians.

The whole-body (tachymetabolic) endothermy seen in modern birds and mammals is long held to have evolved independently in each group, a reasonable assumption when it was believed that its earliest appearances in birds and mammals arose many millions of years apart. That assumption is consistent with current acceptance that the non-shivering thermogenesis (NST) component of regulatory body heat originates differently in each group: from skeletal muscle in birds and from brown adipose tissue (BAT) in mammals. However, BAT is absent in monotremes, marsupials, and many eutherians, all whole-body endotherms. Indeed, recent research implies that BAT-driven NST originated more recently and that the biochemical processes driving muscle NST in birds, many modern mammals and the ancestors of both may be similar, deriving from controlled 'slippage' of Ca2+ from the sarcoplasmic reticulum Ca2+ -ATPase (SERCA) in skeletal muscle, similar to a process seen in some fishes. This similarity prompted our realisation that the capacity for whole-body endothermy could even have pre-dated the divergence of Amniota into Synapsida and Sauropsida, leading us to hypothesise the homology of whole-body endothermy in birds and mammals, in contrast to the current assumption of their independent (convergent) evolution. To explore the extent of similarity between muscle NST in mammals and birds we undertook a detailed review of these processes and their control in each group. We found considerable but not complete similarity between them: in extant mammals the 'slippage' is controlled by the protein sarcolipin (SLN), in birds the SLN is slightly different structurally and its role in NST is not yet proved. However, considering the multi-millions of years since the separation of synapsids and diapsids, we consider that the similarity between NST production in birds and mammals is consistent with their whole-body endothermy being homologous. If so, we should expect to find evidence for it much earlier and more widespread among extinct amniotes than is currently recognised. Accordingly, we conducted an extensive survey of the palaeontological literature using established proxies. Fossil bone histology reveals evidence of sustained rapid growth rates indicating tachymetabolism. Large body size and erect stature indicate high systemic arterial blood pressures and four-chambered hearts, characteristic of tachymetabolism. Large nutrient foramina in long bones are indicative of high bone perfusion for rapid somatic growth and for repair of microfractures caused by intense locomotion. Obligate bipedality appeared early and only in whole-body endotherms. Isotopic profiles of fossil material indicate endothermic levels of body temperature. These proxies led us to compelling evidence for the widespread occurrence of whole-body endothermy among numerous extinct synapsids and sauropsids, and very early in each clade's family tree. These results are consistent with and support our hypothesis that tachymetabolic endothermy is plesiomorphic in Amniota. A hypothetical structure for the heart of the earliest endothermic amniotes is proposed. We conclude that there is strong evidence for whole-body endothermy being ancient and widespread among amniotes and that the similarity of biochemical processes driving muscle NST in extant birds and mammals strengthens the case for its plesiomorphy.

The roles of diffusion and convection in ventilation of animal burrows.

The relationship between body mass and the respiratory microenvironment of burrowing animals is examined using artificial burrows containing surrogate animals that simulate O2 consumption by removal of air and simultaneous replacement with N2. Allometric relationships between body mass and burrow radius, nest chamber radius, and O2 consumption rate show that published mathematical predictions of diffusion-mediated gas exchange are adequate to describe the respiratory environments of animals in small blind-ending burrows through porous substrata. Diffusion is sufficient to ventilate burrows containing small mammals weighing less than 340 g, or subterranean nest chambers connected to the surface by one or more tunnels containing mammals weighing less than 30 kg. Outside of these limits, convection prevails and prevents the development of hypoxic conditions, particularly in burrows of mammals weighing more than 1300 g.

Regional femoral bone blood flow rates in laying and non-laying chickens estimated with fluorescent microspheres.

The metabolic rate of vertebrate bone tissue is related to bone growth, repair and homeostasis, which are all dependent on life stage. Bone metabolic rate is difficult to measure directly, but absolute blood flow rate () should reflect local tissue oxygen requirements. A recent 'foramen technique' has derived an index of blood flow rate () by measuring nutrient foramen sizes of long bones. is assumed to be proportional to ; however, the assumption has never been tested. This study used fluorescent microsphere infusion to measure femoral bone in anaesthetized non-laying hens, laying hens and roosters. Mean mass-specific cardiac output was 338±38 ml min-1 kg-1, and the two femora received 0.63±0.10% of this. Laying hens had higher wet bone mass-specific to femora (0.23±0.09 ml min-1 g-1) than the non-laying hens (0.12±0.06 ml min-1 g-1) and roosters (0.14±0.04 ml min-1 g-1), presumably associated with higher bone calcium mobilization during eggshell production. Estimated metabolic rate of femoral bone was 0.019 ml O2 min-1 g-1. Femoral increased significantly with body mass, but was not correlated with nutrient foramen radius (r), probably because of a narrow range in foramen radius. Over all 18 chickens, femoral shaft was 1.07±0.30 ml min-1 mm-1. Mean in chickens was significantly higher than predicted by an allometric relationship for adult cursorial bird species, possibly because the birds were still growing.

Gas exchange and dive behaviour in the diving beetle Platynectes decempunctatus (Coleoptera: Dytiscidae).

Many aquatic insects use bubbles on the body surface to store and supply O2 for their dives. There are two types of bubbles: air stores, which store O2 gained from air at the surface, and gas gills that allow passive extraction of O2 from water. Many insects using air stores and gas gills return to the surface to replenish their bubbles and, therefore, their requirement for O2 influences dive behaviour. In this study, we investigate gas exchange and dive behaviour in the diving beetle Platynectes decempunctatus that uses a sub-elytral air store and a small compressible gas gill. We measure the PO2 within the air store during tethered dives, as well as the amount of O2 exchanged during surfacing events. Buoyancy experiments monitor the volume of gas in the gas gill and how it changes during dives. We also directly link O2-consumption rate at three temperatures (10, 15 and 20 °C) with dive duration, surfacing frequency and movement activity. These data are incorporated in a gas exchange model, which shows that the small gas gill of P. decempunctatus contributes less than 10% of the total O2 used during the dive, while up to 10% is supplied by cutaneous uptake.

Extreme hypoxia and high lactate concentrations in early chicken embryos show that cutaneous oxygen uptake is limited by diffusion and metabolism is partially anaerobic.

Respiratory gas exchange in avian embryos progresses through three stages inside the egg. During the first 3-5 days of incubation, the chicken embryo has no specialised respiratory organs and is not reliant on blood circulation. At this stage, it obtains oxygen mainly by diffusion through the eggshell, albumen, amniotic fluid and embryonic tissues. In the second stage, gas exchange relies on diffusion through the shell in the gas phase and convection by blood circulation through the chorioallantoic membrane and body. Day 19 starts the third stage, the transition from chorioallantoic to pulmonary gas exchange, which is complete when the chick hatches on day 20. Metabolism is thought to be aerobic throughout incubation, although the early embryo is covered by fluids (albumen and amniotic fluid) which would greatly resist oxygen diffusion. This study uses fibre-optic sensors to measure oxygen partial pressure (PO2) near, and inside of, the embryo during days 3-5, and relates the data to total body lactate levels. The study shows that fluids surrounding the embryo greatly impede oxygen diffusion, with PO2 becoming severely hypoxic near the embryo, occasionally almost anoxic inside it. Meanwhile, lactate rises to high levels, and the stored lactate can be later oxidised by the embryo when the chorioallantois takes over and metabolism becomes entirely aerobic.

Ontogenetic scaling of the gastrointestinal tract of a marsupial foregut fermenter, the western grey kangaroo Macropus fuliginosus melanops.

As an animal grows, the relative sizes of their organs may grow proportionately or disproportionately, depending on ontogenetic changes in function. If organ growth is proportional (isometric), then the exponent of the scaling equation is 1.0. Relative decreases or increases in size result in exponents less than 1 (hypoallometric) or greater than 1 (hyperallometric). Thus, the empirical exponent can indicate potential changes in function. The entire gastrointestinal tract (GIT) of the foregut-fermenting western grey kangaroo Macropus fuliginosus melanops exhibited biphasic allometry across five orders of magnitude body mass (Mb; 52.0 g-70.5 kg). Prior to weaning at around 12 kg Mb, the entire empty GIT mass scaled with hyperallometry (Mb1.13), shifting to hypoallometry (Mb0.80) post-weaning. In addition, there were varying patterns of hyper-, hypo-, and isometric scaling for select GIT organs, with several displaying phase shifts associated with major life-history events, specifically around exit from the maternal pouch and around weaning. Mass of the kangaroo forestomach, the main fermentation site, scaled with hyperallometry (Mb1.16) before the stage of increased vegetation intake, and possibly after this stage (Mb1.12; P = 0.07), accompanied by a higher scaling factor (elevation of the curve) probably associated with more muscle for processing fibrous vegetation. The acid hindstomach mass showed hyperallometry (Mb1.15) before weaning, but hypoallometry (Mb0.58) post-weaning, presumably associated with decreasing intake of milk. Small intestine mass and length each scaled isometrically throughout ontogeny, with no discernible breakpoints at any life-history stage. The caecum and colon mass were steeply hyperallometric early in-pouch life (Mb1.59-1.66), when the young were ectothermic, hairless, and supported solely by milk. After around 295 g Mb, caecum mass remained hyperallometric (Mb1.14), possibly supporting its early development as a nidus for microbial populations to provide for secondary fermentation in this organ after the young transition from milk to vegetation.

Blood flow rate and wall shear stress in seven major cephalic arteries of humans.

Blood flow rate ( Q˙ ) in relation to arterial lumen radius (ri ) is commonly modelled according to theoretical equations and paradigms, including Murray's Law ( Q˙ ∝ ri3 ) and da Vinci's Rule ( Q˙ ∝ ri2 ). Wall shear stress (τ) is independent of ri with Murray's Law (τ âˆ  ri0 ) and decreases with da Vinci's Rule (τ âˆ  ri-1 ). These paradigms are tested empirically with a meta-analysis of the relationships between Q˙ and ri in seven major arteries of the human cephalic circulation from 19 imaging studies in which both variables were presented. The analysis shows that Q˙ ∝ ri2.16 and τ âˆ  ri-1.02 , more consistent with da Vinci's Rule than Murray's Law. This meta-analysis provides standard values for Q˙ , ri and τ in the human cephalic arteries that may be a useful baseline in future investigations. On average, the paired internal carotid arteries supply 75%, and the vertebral arteries supply 25%, of total brain blood flow. The internal carotid arteries contribute blood entirely to the anterior and middle cerebral arteries and also partly to the posterior cerebral arteries via the posterior communicating arteries of the circle of Willis. On average, the internal carotid arteries provide 88% of the blood flow to the cerebrum and the vertebral arteries only 12%.

Bone foramen dimensions and blood flow calculation: best practices.

Some blood vessels enter bones through foramina, leaving the size of the foramen as a gauge for estimating the rate of blood flow and hence the metabolic rate of the supplied tissues. Foramen dimensions have been measured using varied methods in previous foramen studies, to relate regional blood flows with associated physiological processes. With the increasing interests in this 'foramen technique', standard methods with minimized measurement errors are therefore required. This study provides details of microphotographic and micro-computerized tomographic methods, and introduces a new alternative method, which uses impression material to measure foramen dimensions. The three methods are compared and the results indicate that all of them are capable of obtaining precise and accurate foramen dimension values, although they all have limitations. A microphotograph of the external opening is suggested to be the standard method because of its ease of use, but the alternative methods provide more detailed information on foramen shape. If the foramen is mainly occupied by one artery, blood flow rates can be calculated from foramen size and artery wall-lumen ratio, which is evaluated from the literature survey in this study. If veins or nerves also penetrate the foramen, a relative index of blood flow rate is nevertheless possible for comparative purposes.

Cerebral blood flow rates in recent great apes are greater than in Australopithecus species that had equal or larger brains.

Brain metabolic rate (MR) is linked mainly to the cost of synaptic activity, so may be a better correlate of cognitive ability than brain size alone. Among primates, the sizes of arterial foramina in recent and fossil skulls can be used to evaluate brain blood flow rate, which is proportional to brain MR. We use this approach to calculate flow rate in the internal carotid arteries (Q˙ICA), which supply most of the primate cerebrum. Q˙ICA is up to two times higher in recent gorillas, chimpanzees and orangutans compared with 3-million-year-old australopithecine human relatives, which had equal or larger brains. The scaling relationships between Q˙ICA and brain volume (Vbr) show exponents of 1.03 across 44 species of living haplorhine primates and 1.41 across 12 species of fossil hominins. Thus, the evolutionary trajectory for brain perfusion is much steeper among ancestral hominins than would be predicted from living primates. Between 4.4-million-year-old Ardipithecus and Homo sapiens, Vbr increased 4.7-fold, but Q˙ICA increased 9.3-fold, indicating an approximate doubling of metabolic intensity of brain tissue. By contrast, Q˙ICA is proportional to Vbr among haplorhine primates, suggesting a constant volume-specific brain MR.

Novel vascular plexus in the head of a sea snake (Elapidae, Hydrophiinae) revealed by high-resolution computed tomography and histology.

Novel phenotypes are often linked to major ecological transitions during evolution. Here, we describe for the first time an unusual network of large blood vessels in the head of the sea snake Hydrophis cyanocinctus. MicroCT imaging and histology reveal an intricate modified cephalic vascular network (MCVN) that underlies a broad area of skin between the snout and the roof of the head. It is mostly composed of large veins and sinuses and converges posterodorsally into a large vein (sometimes paired) that penetrates the skull through the parietal bone. Endocranially, this blood vessel leads into the dorsal cerebral sinus, and from there, a pair of large veins depart ventrally to enter the brain. We compare the condition observed in H. cyanocinctus with that of other elapids and discuss the possible functions of this unusual vascular network. Sea snakes have low oxygen partial pressure in their arterial blood that facilitates cutaneous respiration, potentially limiting the availability of oxygen to the brain. We conclude that this novel vascular structure draining directly to the brain is a further elaboration of the sea snakes' cutaneous respiratory anatomy, the most likely function of which is to provide the brain with an additional supply of oxygen.

Cutaneous respiration by diving beetles from underground aquifers of Western Australia (Coleoptera: Dytiscidae).

Insects have a gas-filled respiratory system, which provides a challenge for those that have become aquatic secondarily. Diving beetles (Dytiscidae) use bubbles on the surface of their bodies to supply O2 for their dives and passively gain O2 from the water. However, these bubbles usually require replenishment at the water's surface. A highly diverse assemblage of subterranean dytiscids has evolved in isolated calcrete aquifers of Western Australia with limited/no access to an air-water interface, raising the question of how they are able to respire. We explored the hypothesis that they use cutaneous respiration by studying the mode of respiration in three subterranean dytiscid species from two isolated aquifers. The three beetle species consume O2 directly from the water, but they lack structures on their bodies that could have respiratory function. They also have a lower metabolic rate than other insects. O2 boundary layers surrounding the beetles are present, indicating that O2 diffuses into the surface of their bodies via cutaneous respiration. Cuticle thickness measurements and other experimental results were incorporated into a mathematical model to understand whether cutaneous respiration limits beetle size. The model indicates that the cuticle contributes considerably to resistance in the O2 cascade. As the beetles become larger, their metabolic scope narrows, potentially limiting their ability to allocate energy to mating, foraging and development at sizes above approximately 5 mg. However, the ability of these beetles to utilise cutaneous respiration has enabled the evolution of the largest assemblage of subterranean dytiscids in the world.

Scaling of cardiac morphology is interrupted by birth in the developing sheep Ovis aries.

Scaling of the heart across development can reveal the degree to which variation in cardiac morphology depends on body mass. In this study, we assessed the scaling of heart mass, left and right ventricular masses, and ventricular mass ratio, as a function of eviscerated body mass across fetal and postnatal development in Horro sheep Ovis aries (~50-fold body mass range; N = 21). Whole hearts were extracted from carcasses, cleaned, dissected into chambers and weighed. We found a biphasic relationship when heart mass was scaled against body mass, with a conspicuous 'breakpoint' around the time of birth, manifest not by a change in the scaling exponent (slope), but rather a jump in the elevation. Fetal heart mass (g) increased with eviscerated body mass (Mb , kg) according to the power equation 4.90 Mb0.88 ± 0.26 (± 95%CI) , whereas postnatal heart mass increased according to 10.0 Mb0.88 ± 0.10 . While the fetal and postnatal scaling exponents are identical (0.88) and reveal a clear dependence of heart mass on body mass, only the postnatal exponent is significantly less than 1.0, indicating the postnatal heart becomes a smaller component of body mass as the body grows, which is a pattern found frequently with postnatal cardiac development among mammals. The rapid doubling in heart mass around the time of birth is independent of any increase in body mass and is consistent with the normalization of wall stress in response to abrupt changes in volume loading and pressure loading at parturition. We discuss variation in scaling patterns of heart mass across development among mammals, and suggest that the variation results from a complex interplay between hard-wired genetics and epigenetic influences.

Interspecific scaling of blood flow rates and arterial sizes in mammals.

This meta-study investigated the relationships between blood flow rate (Q̇; cm3 s-1), wall shear stress (τw; dyn cm-2) and lumen radius (ri; cm) in 20 named systemic arteries of nine species of mammals, ranging in mass from 23 g mice to 652 kg cows, at rest. In the dataset, derived from 50 studies, lumen radius varied between 3.7 µm in a cremaster artery of a rat and 11.2 mm in the aorta of a human. The 92 logged data points of [Formula: see text] and ri are described by a single second-order polynomial curve with the equation: [Formula: see text] The slope of the curve increased from approximately 2 in the largest arteries to approximately 3 in the smallest ones. Thus, da Vinci's rule ([Formula: see text]) applies to the main arteries and Murray's law ([Formula: see text]) applies to the microcirculation. A subset of the data, comprising only cephalic arteries in which [Formula: see text] is fairly constant, yielded the allometric power equation: [Formula: see text] These empirical equations allow calculation of resting perfusion rates from arterial lumen size alone, without reliance on theoretical models or assumptions on the scaling of wall shear stress in relation to body mass. As expected, [Formula: see text] of individual named arteries is strongly affected by body mass; however, [Formula: see text] of the common carotid artery from six species (mouse to horse) is also sensitive to differences in whole-body basal metabolic rate, independent of the effect of body mass.

Ameliorating the adverse cardiorespiratory effects of chemical immobilization by inducing general anaesthesia in sheep and goats: implications for physiological studies of large wild mammals.

Chemical immobilization is necessary for the physiological study of large wild animals. However, the immobilizing drugs can adversely affect the cardiovascular and respiratory systems, yielding data that do not accurately represent the normal, resting state. We hypothesize that these adverse effects can be ameliorated by reversing the immobilizing agent while holding the animal under general anaesthesia. We used habituated sheep Ovis aries (N = 5, 46.9 ± 5.3 kg body mass, mean ± SEM) and goats Capra hircus (N = 4, 27.7 ± 2.8 kg) as ungulate models for large wild animals, and measured their cardiorespiratory function under three conditions: (1) mild sedation (midazolam), as a proxy for the normal resting state, (2) immobilization (etorphine and azaperone), and (3) general anaesthesia (propofol) followed by etorphine antagonism (naltrexone). Cardiac output for both sheep and goats remained unchanged across the three conditions (overall means of 6.2 ± 0.9 and 3.3 ± 0.3 L min-1, respectively). For both sheep and goats, systemic and pulmonary mean arterial pressures were significantly altered from initial midazolam levels when administered etorphine + azaperone, but those arterial pressures were restored upon transition to propofol anaesthesia and antagonism of the etorphine. Under etorphine + azaperone, minute ventilation decreased in the sheep, though this decrease was corrected under propofol, while the minute ventilation in the goats remained unchanged throughout. Under etorphine + azaperone, both sheep and goats displayed arterial blood hypoxia and hypercapnia (relative to midazolam levels), which failed to completely recover under propofol, indicating that more time might be needed for the blood gases to be adequately restored. Nonetheless, many of the confounding cardiorespiratory effects of etorphine were ameliorated when it was antagonized with naltrexone while the animal was held under propofol, indicating that this procedure can largely restore the cardiovascular and respiratory systems closer to a normal, resting state.

Scaling of morphology and ultrastructure of hearts among wild African antelope.

The hearts of smaller mammals tend to operate at higher mass-specific mechanical work rates than those of larger mammals. The ultrastructural characteristics of the heart that allow for such variation in work rate are still largely unknown. We have used perfusion-fixation, transmission electron microscopy and stereology to assess the morphology and anatomical aerobic power density of the heart as a function of body mass across six species of wild African antelope differing by approximately 20-fold in body mass. The survival of wild antelope, as prey animals, depends on competent cardiovascular performance. We found that relative heart mass (g kg-1 body mass) decreases with body mass according to a power equation with an exponent of -0.12±0.07 (±95% confidence interval). Likewise, capillary length density (km cm-3 of cardiomyocyte), mitochondrial volume density (fraction of cardiomyocyte) and mitochondrial inner membrane surface density (m2 cm-3 of mitochondria) also decrease with body mass with exponents of -0.17±0.16, -0.06±0.05 and -0.07±0.05, respectively, trends likely to be associated with the greater mass-specific mechanical work rate of the heart in smaller antelope. Finally, we found proportionality between quantitative characteristics of a structure responsible for the delivery of oxygen (total capillary length) and those of a structure that ultimately uses that oxygen (total mitochondrial inner membrane surface area), which provides support for the economic principle of symmorphosis at the cellular level of the oxygen cascade in an aerobic organ.