Maximal aerobic performance of deer mice in combined cold and exercise challenges.

In nature, animals frequently need to deal with several physiological challenges simultaneously. We examined thermoregulatory performance (body temperature stability) and maximal oxygen consumption of deer mice (Peromyscus maniculatus) during intense exercise at room temperature, acute cold exposure, and exercise during cold exposure. Results with exercise and cold exposure alone were consistent with previous studies: there was little difference between maximal metabolism elicited by exercise alone or cold exposure alone in warm-acclimated mice; after cold acclimation (9 weeks at 5 degrees C), maximal exercise metabolism did not change but maximum thermogenic capacity increased by >60%. Warm acclimated animals did not increase maximal oxygen consumption when exercise was combined with moderate cold (0 degrees C) and had decreased maximal oxygen consumption when exercise was combined with severe cold (-16 degrees C). Combined cold and exercise also decreased thermoregulatory performance and exercise endurance time. Cold acclimation improved thermoregulatory performance in combined cold and exercise, and there was also a slight increase in endurance. However, as for warm-acclimated animals, maximal exercise metabolism did not increase at low temperatures. We interpret these results as an indication of competition between thermoregulatory and locomotor effectors (brown adipose tissue and skeletal muscle) under the combined challenges of cold exposure and maximal exercise, with priority given to the locomotor function.

Developmental plasticity in aerobic performance in deer mice (Peromyscus maniculatus).

While several studies have examined the abiotic effects of altitude (low ambient temperatures and hypoxia) on the aerobic performance of small mammals, few have explored the effects of development and maturation at different altitudes on aerobic performance as adults. We examined the basal metabolism and aerobic performance of deer mice (Peromyscus maniculatus) under four different developmental and testing regimes: (1) reared (gestation through weaning) and tested at high altitude; (2) reared and tested at low altitude; (3) reared at low altitude and tested at high altitude after acclimation; and (4) reared at low altitude and tested in hypoxia without acclimation. We found that mice that developed and were tested at low altitudes had a higher aerobic capacity (both aerobic performance and basal metabolic rate) than those that developed, or were acclimated as adults, at high altitudes. In addition, we found that mice that developed at high altitude did not have a higher aerobic capacity than those that developed at low altitude and were acclimated to high altitude as adults. Both groups tested at high altitudes had higher hematocrits (% red blood cells) and hemoglobin than mice tested at low altitudes. Surprisingly, mice acclimated to low altitudes and given an instantaneous exposure to hypoxia did not suffer a depression in aerobic performance.

Effects of altitude and temperature on organ phenotypic plasticity along an altitudinal gradient.

Small mammals living in high-altitude environments must endure decreased ambient temperatures and hypoxic conditions relative to sea-level environments. Previously, it was noted that heart, lung and digestive tract masses and blood hematocrit increase along an altitudinal gradient in small mammals. Increases in digestive organ mass were attributed to lower ambient temperatures and greater food intake, and increases in lung mass and hematocrit were attributed to hypoxia, but these assumptions were not explicitly tested. In addition, it was not clear whether changes in heart and lung mass were a function of an increase in organ blood content or of an increase in organ tissue mass. We used captive deer mice (Peromyscus maniculatus sonoriensis) to determine the relative effects of ambient temperature and oxygen concentration (PO2) on organ mass and blood hematocrit along an altitudinal gradient. We also exsanguinated hearts and lungs to determine whether changes in mass were associated with the blood content or with increases in tissue mass. We found that small intestine mass was, as expected, correlated positively with energy intake and negatively with ambient temperature. Heart mass was also negatively correlated with temperature. Lung mass and hematocrit were, as expected, positively correlated with altitude (and PO2). Interestingly, the masses of both small intestine and kidney were negatively correlated with altitude. For kidney mass, this correlation was apparent in cold-exposed mice but not in warm-exposed mice. We also found that changes in both heart and lung mass were mainly a function of changes in tissue mass rather than blood content. These data show that different abiotic variables have different effects on organ masses at high altitude, but also that phenotypic plasticity in response to cold temperatures and low oxygen pressures at altitude is widespread across several different organ systems, suggesting a general elevated whole-body response.

Parasite infection and caloric restriction induce physiological and morphological plasticity.

To investigate the effects of parasitism and caloric restriction on morphology (body composition, organ mass) and physiology (resting metabolism, intestinal glucose transport capacity), we gave laboratory mice intestinal parasites (Heligmosomoides polygyrus, Nematoda), 30% caloric restriction, or both. Calorically restricted mice had smaller body mass, enhanced glucose transport capacity, and lower resting metabolism than ad libitum-fed mice. Parasitized mice maintained body mass, had diminished intestinal glucose transport capacity, and greater resting metabolism than unparasitized mice. Parasitized, calorically restricted mice had smaller organ masses than parasitized, ad libitum-fed mice and did not increase their glucose uptake rate as much as unparasitized, calorically restricted mice. There was a significant interaction between caloric restriction and parasite status for morphological variables but not for physiological variables. Knowing the types of phenotypic changes that occur with simultaneous parasitism and caloric restriction will provide insight into understanding human helminthiasis in food-restricted communities and also how wild animals cope with environments where parasitism and seasonal food restriction are common.

Responses to lactation and cold exposure by deer mice (Peromyscus maniculatus).

Recently, much interest has been expressed in understanding how animals use phenotypic plasticity of tissue size and function to meet increased metabolic demands. We set out to learn (i) whether female deer mice (Peromyscus maniculatus) given lactation (two to seven pups per litter), cold (5 degrees C), or cold plus lactation as energy demands display phenotypic plasticity in organ size and function; (ii) whether that plasticity is similar to laboratory mice given the same demands; and (iii) whether lactational performance in deer mice is derived from limits on central or peripheral organs. We found that deer mice responded to lactation by increasing digestible food intake and increasing the masses of the stomach, small intestine, cecum and liver, and the length of the small intestine. Heart mass was lower in lactating than in nonlactating mice. Cold exposure also caused increases in digestible food intake and increases in the masses of the small intestine, kidney, and heart. We conclude that deer mice display organ tissue plasticity in response to both lactation and cold exposure in a similar manner to laboratory mice. We also conclude that deer mice are not limited by central processing organs because they are able to increase digestive organ size continuously with increased energetic demands.

Combined effects of cold exposure and sub-lethal intestinal parasites on host morphology and physiology.

Multiple, simultaneous demands elicit physiological and morphological responses that may jeopardize an animal's ability to respond to future challenges, especially when resources are limited. Laboratory mice (Mus musculus) experimentally infected with an intestinal nematode (Heligmosomoides polygyrus) and then exposed to cold showed phenotypic plasticity of morphological and physiological responses. The parasitized mice maintained a similar body mass to the unparasitized mice but had less body fat and showed changes in some organ masses, a greater resting metabolic rate (RMR) and a diminished glucose uptake capacity both at the site of infection and in regions of the small intestine not occupied by parasites. Cold-exposed mice had a greater RMR, less body fat, a greater glucose transport capacity and showed changes in organ masses compared with mice maintained at room temperature. The responses to cold exposure were not affected by parasitism for any dependent variable. The costs of having parasites during simultaneous cold exposure included decreased energy reserves and greater maintenance requirements, which may then decrease the energy available for future expenditures, such as reproduction.

The mechanistic basis of aerobic performance variation in red junglefowl.

We examined aerobic performance, organ and muscle mass and enzymatic activity in red junglefowl (Gallus gallus). We tested three models of performance limitation (central limits, peripheral limits, symmorphosis) and explored relationships between basal metabolic rate (BMR), aerobic capacity ( V (O2max)) and social rank. Males had a lower BMR, a higher V (O2max) and a greater aerobic scope than females. Females possessed larger peritoneal and reproductive organs, while males had larger hearts, lungs and leg muscles. In females, BMR was correlated with spleen mass and V (O2max) was correlated with hematocrit and large intestine mass. Male BMR was correlated with intestinal tract and lung mass, and V (O2max) was correlated with heart and pectoralis mass. Male citrate synthase activity averaged 57 % higher than that of females and was correlated with V (O2max) (this correlation was not significant in females). Female social status was not correlated with any variable, but male dominance was associated with higher aerobic scope, larger heart and lungs, smaller peritoneal organs and greater leg citrate synthase activity. We conclude that aerobic capacity is controlled by system-wide limitations (symmorphosis) in males, while in females it is controlled by central organs. In neither sex is elevated aerobic capacity associated with increased maintenance costs.

Morphological and physiological responses to altitude in deer mice Peromyscus maniculatus.

Individuals within a species, living across a wide range of habitats, often display a great deal of phenotypic plasticity for organ mass and function. We investigated the extent to which changes in organ mass are variable, corresponding to environmental demand, across an altitudinal gradient. Are there changes in the mass of oxygen delivery organs (heart and lungs) and other central processing organs (gut, liver, kidney) associated with an increased sustainable metabolic rate that results from decreased ambient temperatures and decreased oxygen availability along an altitudinal gradient? We measured food intake, resting metabolic rate (RMR), and organ mass in captive deer mice (Peromyscus maniculatus bairdii) at three sites from 1,200 to 3,800 m above sea level to determine whether energy demand was correlated with organ mass. We found that food intake, gut mass, and cardiopulmonary organ mass increased in mice living at high altitudes. RMR was not correlated with organ mass differences along the altitudinal gradient. While the conditions in this study were by no means extreme, these results show that mice living at high altitudes have higher levels of energy demand and possess larger cardiopulmonary and digestive organs than mice living at lower altitudes.

The effects of increased protein intake on kidney size and function.

In endothermic vertebrates, long-term increases in metabolic energy demand are often associated with increases in food intake and accompanied by increases in organ mass. Wide-scale increases in organ mass have often been attributed to a metabolic response to increased energy intake and utilization. On a constant diet, however, increased food intake is also associated with increased protein intake. We hypothesized that, while increased food intake itself may be responsible for increases in digestive tract mass, the consequent increased protein intake would be the factor responsible for increased kidney mass and function. Thus, we exposed male and female mice to diets differing in protein level (7 %, 15 % or 46 % casein by mass) at different acclimation temperatures (5 degrees C or 23 degrees C). Within an acclimation temperature, food intake rate remained constant over the entire range of dietary protein level, and protein intake rate increased as dietary content increased. The mice in the cold-acclimation group increased food intake rate by 48-120 % over those in the warm-acclimation group. Liver, kidney and stomach mass increased with protein intake rate, while digestive tract and other vital organ masses increased only in response to increased energy intake rate. Blood urea nitrogen levels increased with protein intake rate. Glomerular filtration rates increased with increases in dietary protein level in male mice but not female mice. Finally nitrogen filtration rate increased with protein intake rate for mice on the high-protein diet. We suggest that it is primarily the increased protein intake rate rather than the increased food intake rate that results in the changes in kidney and liver mass and kidney function observed to occur in situations of high energy demand.

Adaptation of the maternal intestine during lactation.

One of the most dramatic adaptations to lactation is a large increase in the size and complexity of maternal intestine. Although there are few data on changes in intestinal size, intestinal enlargement has been observed in many taxonomic groups. In this review I describe the morphological and physiological changes in the intestinal mass of lactating animals and discuss their functional significance. The observed increases maintain the digestive efficiency of the food, as well as insure adequate absorption of nutrients in the face of the increased energy demand that accompanies lactation. The extent of the increase in size is proportional to the increase in energy demand. It is clear that if the intestine did not accommodate during lactation mothers would not have the capacity to absorb the nutrients need to maintain their energy demand.

Maximal sustained energy budgets in humans and animals.

Why are sustained energy budgets of humans and other vertebrates limited to not more than about seven times resting metabolic rate? The answer to this question has potential applications to growth rates, foraging ecology, biogeography, plant metabolism, burn patients and sports medicine.

Simultaneous manipulation of intestinal capacities and nutrient loads in mice.

To study the relationship between capacity and load in the small intestine, we simultaneously varied dietary nutrient load and intestinal capacity in mice. Intestinal transection alone caused an increase in intestinal mass, because of increased serosal mass. Because virgin mouse intestine possesses 180% reserve uptake capacity before resection and the intestine regenerates after resection, resection of up to 50% had no effect on food intake, digestive efficiency, intestinal brush-border glucose uptake rate, or mass of all organs measured except the cecum. Regeneration of intestinal mass and glucose uptake capacity was quantitatively complete, because intestinal mass 10 wk after resection was similar to that in unresected mice. Resected intestinal mass in lactating mice was four times larger than that immediately after resection in virgin mice. Cecal mass increased in 50%-resected lactating mice with high food intakes, suggesting nutrient spillage into the distal gut as a signal for regeneration. Mice failed to survive 70% resection of the intestine, possibly because intestinal reserve uptake capacity was exhausted immediately after surgery, making regeneration impossible.

Is mammary output capacity limiting to lactational performance in mice?

Using lactation in mice as a model, we sought to determine whether ceilings on sustained energy expenditure reside in the capacities of energy-acquiring and input organs (such as the intestine) or of energy-expending and output organs (such as the mammary glands). To distinguish between these possibilities experimentally, we surgically varied the teat number of lactating mother mice while simultaneously varying their litter size. The energy burden on each teat (i.e. the pup/teat ratio) could thus be varied independently of the energy burden (i.e. litter size) on the mother herself or on her intestine. At each teat number, pup mass proved to be maximal at intermediate litter sizes. At a given pup/teat ratio, mothers with five teats weaned pups no larger than the pups of normal (10-teat) mothers, even though the total energy burden on the former mothers was only half as large. Mothers with only two teats could not wean any pups. Litter size controlled maternal food intake, which in turn controlled intestinal mass and nutrient uptake capacity. Disproportionately high food intake for the smallest litters appears to reflect capital start-up costs of lactation. Pup mass is evidently limited by inadequate suckling stimulation of mammary glands.

Computer support for clinical and ancillary support areas.

Military medicine is aggressively meeting the need for enhanced information flow and improved efficiency in the delivery of health care by implementing automated systems. A Department of Defense (DOD) Agency, the Tri-Service Medical Information Systems (TRIMIS) Program office, is centrally procuring automated data processing to support clinical and patient appointment activities within the DOD health care system of 165 hospitals and 287 clinics. The procured systems are then implemented with the assistance of the military departments. Systems are now supporting cardiology, pharmacy, radiology, clinical laboratory, and patient appointment and scheduling. Capabilities of all these systems are detailed in the paper. To date, the TRIMIS efforts have contributed significantly to more efficient information processing, thus ensuring continued quality health care through the DOD.