Physiological Parameter Values for Physiologically Based Pharmacokinetic Models

Summary 1. The role of energy in ecological processes has hitherto been considered primarily from the standpoint that energy supply is limited. That is, traditional resource-based ecological and evolutionary theories and the recent ‘metabolic theory of ecology’ (MTE) all assume that energetic constraints operate on the supply side of the energy balance equation. 2. For endothermic animals, we provide evidence suggesting that an upper boundary on total energy expenditure is imposed by the maximal capacity to dissipate body heat and therefore avoid the detrimental consequences of hyperthermia – the heat dissipation limit (HDL) theory. We contend that the HDL is a major constraint operating on the expenditure side of the energy balance equation, and that processes that generate heat compete and trade-off within a total boundary defined by heat dissipation capacity, rather than competing for limited energy supply. 3. The HDL theory predicts that daily energy expenditure should scale in relation to body mass (Mb) with an exponent of about 0AE63. This contrasts the prediction of the MTE of an exponent of 0AE75. 4. We compiled empirical data on field metabolic rate (FMR) measured by the doubly-labelled water method, and found that they scale to Mb with exponents of 0AE647 in mammals and 0AE658 in birds, not significantly different from the HDL prediction (P >0 AE05) but lower than predicted by the MTE (P <0 AE001). The same statistical result was obtained using phylogenetically independent contrasts analysis. Quantitative predictions of the model matched the empirical data for both mammals and birds. There was no indication of curvature in the relationship between Loge FMR and Loge Mb. 5. Together, these data provide strong support for the HDL theory and allow us to reject the MTE, at least when applied to endothermic animals. 6. The HDL theory provides a novel conceptual framework that demands a reframing of our views of the interplay between energy and the environment in endothermic animals, and provides many new interpretations of ecological and evolutionary phenomena.

https://besjournals.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2656.2010.01689.x

Maximal heat dissipation capacity and hyperthermia risk: neglected key factors in the ecology of endotherms

The process of weaning is related to a critical or threshold body weight attained by offspring among large-bodied mammals; the anthropoid primates, ungulates and pinnipeds. While weaning weight was allometrically related to maternal weight in interspecific comparisons, it was isometrically related to neonatal weight. When a neonate had grown to four times its birth weight, it was weaned. Differences between taxonomic groups were found only among the fasting phocids, where weanlings attained a lower, but proportional, weight. The duration of lactation was only weakly allometrically related to maternal or neonatal weight, and varied between individuals intraspecifically as a function of maternal condition. The time to weaning appears to be ecologically sensitive rather than to reflect interspecific life-history variation, in that, irrespective of the time to weaning, similar proportional weights appear to be attained. Interspecific similarities in threshold weaning weights are suggested to result from constraints on maternal abilities to meet energetic requirements of offspring through lactation after infants attain a threshold weight.

Growth, weaning and maternal investment from a comparative perspective

Summary One challenge for veterinarians, animal facilities and research scientists is the making of physiological estimates appropriate to a variety of species for which data are often either completely lacking or are incomplete. Our intent in compiling the data in this paper is to provide the best possible database of normal physiological and anatomical values primarily (though not exclusively) for four common mammalian model species: mouse, rat, dog and man. In order to make those data as accessible and applicable as possible, we have presented the results of this study in the form of body-size dependent allometric equations in which some variable (Y) is expressed as a dependent function of body mass (M) in the power-law

https://lan.sagepub.com/content/36/1/1.full.pdf

Use of allometry in predicting anatomical and physiological parameters of mammals.

https://www.zora.uzh.ch/id/eprint/3313/2/YJHEV-A-105_Barrickman_et_alV.pdf

Life history costs and benefits of encephalization: a comparative test using data from long-term studies of primates in the wild.

Body weight data, collected routinely from the US Air Force chimpanzee colony at Holloman AFB, was used for a longitudinal analysis of growth. Data were fitted to a model based on human growth patterns, which is described and compared to other treatments applied to growth data. Results are compared to other observations of chimpanzee and of human growth.

Weight growth of colony-reared chimpanzees.

The scaling of metabolic heat production rate on body mass is investigated for five species of small laboratory mammal in order to define selection of animals of metabolic rates and size range appropriate for the measurement of changes in the scaling relationship upon exposure to weightlessness in Shuttle/Spacelab experiment. Metabolic rates were measured according to oxygen consumption and carbon dioxide production for individual male and female Swiss-Webster mice, Syrian hamsters, Simonsen albino rats, Hartley guinea pigs and New Zealand white rabbits, which range in mass from 0.05 to 5 kg mature body size, at ages of 1, 2, 3, 5, 8, 12, 18 and 24 months. The metabolic intensity, defined as the heat produced per hour per kg body mass, is found to decrease dramatically with age until the animals are 6 to 8 months old, with little or no sex difference. When plotted on a logarithmic graph, the relation of metabolic rate to total body mass is found to obey a power law of index 0.676, which differs significantly from the classical value of 0.75. When the values for the mice are removed, however, an index of 0.749 is obtained. It is thus proposed that six male animals, 8 months of age, of each of the four remaining species be used to study the effects of gravitational loading on the metabolic energy requirements of terrestrial animals.

Scaling of metabolic rate on body mass in small laboratory mammals.

Body composition of rats flown aboard Cosmos-1129.

Scale effects in the musculoskeletal system, viscera and skin of small terrestrial mammals.

The hypothesis that increased loading on an animal by chronic centrifugation results in an increase in skeletal mass was tested, using metabolically mature hamsters, rats, guinea pigs, Dutch rabbits and New Zealand rabbits representing a body mass range from 0.15 to 3.8 kg. Groups of 12 male animals of each species were subjeted to 2.0 g for 6 weeks on a 2.74 radius centrifuge with one degree of freedom. Subsequently, six of the animals were killed to measure whole body composition, while the rest comprised the control group, recovering for four weeks at 1.0 g prior to composition analysis. Results show a significant increase in bone mineral mass at 2.0 g. These centrifuge experiment results were then compared with the results of the USSR Cosmos Biosatellite experiment, whereby five rats experienced osteoporosis after 18.5 days of weightlessness. The opposing nature of effects that occurred at 0 g and 2.0 g is indicated schematically of particular interest is the fact that the bone mineral mass of the Cosmos 1129 flight rats was 17 pct less than that of the 1.0 g controls; whereas the bone mineral mass of the centrifuge rats was 18 pct greater than that of their 1.0 g controls. It is concluded that the bone mineral mass of the rat is directly proportional to gravitational loading over the range of 0 g to 2.0 g.

Skeletal mass change as a function of gravitational loading.

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