Long-term cold adaptation in the rat

1. To determine whether long-term cold exposure induces insulative adaptation in the rat, two groups of eight adult animals each were exposed to 4 and 25 degrees C, respectively, for 18 months. 2. At any ambient temperature between -5 and 30 degrees C, the cold adapted animals had a higher rate of oxygen uptake, and higher unfurred skin temperatures than the controls. 3. At ambient temperatures below thermoneutrality, whole body thermal resistance increased continuously in both groups of animals. 4. It is concluded that long-term exposure does not induce insulative adaptation, and that thermal resistance is not maximal at the lower critical temperature.     

Thermoregulatory responses of restrained versus unrestrained rabbits.

Two male and one female New Zealand white rabbits were used in this study. At ambient temperatures of 20, 10, and 0° C, the animals were either lightly restrained with a Plexiglas collar or were unrestrained. Heat balance was zero during these experiments, as indicated by a stable rectal temperature.Heat losses due to vasomotor state and respiratory evaporative water loss were not significantly different between the restrained and unrestrained animals, whereas metabolism and heart rate were significantly higher in the restrained animals. Inappropriate posture, which is caused by the restraint, may be responsible for an increased energy expenditure at low ambient temperatures of as much as 32% of the resting heat production.     

Thyroid gland activity and motor activity during dog ontogenesis]

The locomotor activity (LA) and the level of the protein-bound iodine (PBI) in the blood serum were investigated in 62 puppies at the age of 1--12 months. A parallel elevation of PBI and the LA was observed the first 4 months after birth. The second peak of the LA at the age of 7--9 months was not accompanied by any PBI rise. Inhibition of the thyroid function with mercasolyl increased the LA at the age of 1--3 months and decreased it at the age of 7 months. An increase of the LA one month after thyroidectomy was found at the age of 1 and 3.5 months. The activity of puppies operated on at the age of one month showed a sharp fall after 2--4 months. The data on various effect of thyroid hormones on puppies of different age pointed to the complex relation between the LA and the thyroid gland function.     

Muscle-specific loss of apoptosis-inducing factor leads to mitochondrial dysfunction, skeletal muscle atrophy, and dilated cardiomyopathy

Cardiac and skeletal muscle critically depend on mitochondrial energy metabolism for their normal function. Recently, we showed that apoptosis-inducing factor (AIF), a mitochondrial protein implicated in programmed cell death, plays a role in mitochondrial respiration. However, the in vivo consequences of AIF-regulated mitochondrial respiration resulting from a loss-of-function mutation in Aif are not known. Here, we report tissue-specific deletion of Aif in the mouse. Mice in which Aif has been inactivated specifically in cardiac and skeletal muscle exhibit impaired activity and protein expression of respiratory chain complex I. Mutant animals develop severe dilated cardiomyopathy, heart failure, and skeletal muscle atrophy accompanied by lactic acidemia consistent with defects in the mitochondrial respiratory chain. Isolated hearts from mutant animals exhibit poor contractile performance in response to a respiratory chain-dependent energy substrate, but not in response to glucose, supporting the notion that impaired heart function in mutant animals results from defective mitochondrial energy metabolism. These data provide genetic proof that the previously defined cell death promoter AIF has a second essential function in mitochondrial respiration and aerobic energy metabolism required for normal heart function and skeletal muscle homeostasis.     

Metabolic responses of hibernating golden-mantled ground squirrels Citellus lateralis to lowered environmental temperatures

1. Hibernating C. lateralis were exposed to lowered ambient temperatures in order to investigate the relationship between hibernation stress and the thermoregulatory responses of the animals. 2. The least hibernation-stress squirrels exhibited a passive decline in metabolic rate until their body temperatures stabilized close to microenvironmental temperature. 3. The most stressed individuals aroused from hibernation in response to the declining ambient temperatures. 4. Intermediately stressed animals demonstrated an initial passive decline in temperature; however, at various temperatures (0.3-6.8 degrees C), this group increased their metabolic rate but did not arouse from hibernation.     

The hormonal indices of the reactivity of the central links in the hypothalamo-hypophyseal-adrenocortical system of rats during postnatal ontogeny]

Radioimmunological assay has been made of the amount of ACTH in the adenohypophysis and blood plasma in adult male rats as well as in 1, 3, 5, 7, and 20 days old rat puppies 30 minutes after a surgical stress, i. e. cutting the skin at the back of the body. Reliable increase of ACTH level was originally observed in 7-day puppies, whereas in younger animals surgical stress resulted in the decrease of ACTH in the blood. Changes in vasopressin content of the blood and hypophysis exhibit significant variations, but on the whole mainly the decrease was observed in younger animals together with the increase from the 5-7th day of postnatal development of rats. Accumulation of vasopressin was noted in the median eminence after surgical stress in younger animals. The data obtained suggest that the early period of development of the hypothalamo-hypophyseal-adrenocortical system is characterized rather by paradoxal reaction than by non-reactivity, which may be associated with poor neurohormonal transport in the outer zone of the median eminence.     

Effect of thermal stress and water deprivation on the acetylcholinesterase activity of the pig brain and hypophyses

The effects of direct exposure of boars to thermal stress for 1 h daily for 5 days and to acute water deprivation for 24 or 48 h were studied on the acetylcholinesterase (AChE) activity of porcine brain and hypophysial regions. Mean ambient temperatures, respiratory rates and rectal temperatures in the open were significantly higher than inside the pen. Heat stress induced a rise in AChE activities in the pons, cerebellum, amygdala, hippocampus, hypothalamus, mid-brain and medulla oblongata. However, no significant changes were observed in the cerebral cortex, adenohypophysis and neurohypophysis. Water deprivation significantly (P<0.05) depressed AChE activity to varying extents depending on the duration of water restriction. Thus AChE activity in the amygdala was depressed by water deprivation for 24 h but partially restored at 48 h. The pons and medulla oblongata were comparable to the amygdala in this respect. The adenohypophysis and neurohypophysis were relatively unaffected.     

Effects of microwave exposure and temperature on survival of mice infected with Streptococcus pneumoniae

Female CD-1 mice were injected with an LD₅₀ dose of Streptococcus pneumoniae and then exposed to 2.45 GHz (CW) microwave radiation at an incident power density of 10 mW/cm² (SAR = 6.8 W/kg), 4 h/d for 5 d at ambient temperatures of 19 °C, 22 °C, 25 °C, 28 °C, 31 °C, 34 °C, 37 °C and 40 °C. Four groups of 25 animals were exposed at each temperature with an equal number of animals concurrently sham-exposed. Survival was observed for a 10-d period after infection. Survival of the sham-exposed animals increased as ambient temperature increased from 19 °C–34 °C. At ambient temperatures at or above 37 °C the heat induced in the body exceeded the thermoregulatory capacity of the animals and deaths from hyperthermia occurred. Survival of the microwave-exposed animals was significantly greater than the shams (～20%) at each ambient temperature below 34 °C. Based on an analysis of the data it appears that the hyperthermia induced by microwave exposure may be more effective in increasing survival in infected mice than hyperthermia produced by conventional methods (ie, high ambient temperature). Microwave radiation may be beneficial to infected animals at low and moderate ambient temperatures, but it is detrimental when combined with high ambient temperatures.     

Responses of cattle to the combined exposure to diurnal temperature rhythm (−5 to 25°C) and to simulated high-altitude (4,000 m)

Eight 1/2-year old calves were exposed in a climatized altitude chamber to the following four conditions: 400 and 4,000 m at constant T_a (17°C), 400 and 4,000 m at alternating T_a (–5° to 25°C). Each exposure lasted for 24 h and for the rhythmic conditions included a cold night and warm midday hours, supplemented by infrared heaters. During exposure, hourly measurements were made of heart rate, respiratory rate, rectal and three skin temperatures. Every 3-h blood samples were collected for the determination of 10 blood variables. The following main results were obtained: (a) Altitude alone caused increases in respiratory rate, heart rate, erythrocyte number, haemoglobin, specific gravity of blood and plasma, LDH and all four body temperatures. (b) In the rhythmic exposures, high correlation coefficients were found between ambient temperature on the one hand and skin temperatures (0.88 to 0.94), rectal temperature (–0.43) and respiratory rate (0.49) on the other hand. A change in ambient temperature by 1°C lead, on average, to a change in ear temperature by 1.2°C. (c) in response to falling ambient temperature during the night, rectal temperature and heart rate increased. This was interpreted as indicating a compensatory elevation in meta bolic heat production. At the same time, there was haemoconcentration as shown by elevations in erythrocyte number, haematocrit and haemoglobin. This haemoconcentration might have reflected splenic discharge, possibly supplemented by some loss of water from the plasma. (d) The warm environmental conditions around midday produced mild heat responses in terms of elevated values for respiratory rate, heart rate and body temperatures. (e) It is concluded that the rhythmic temperature with alternating stress of cold and mild heat, especially in combination with high altitude, was a strain on the animals and that they were forced to expend extra energy for combatting altitude- and temperature stress, energy which no longer would be available for productive processes.Presented at the Eight International Congress of Biometeorology, 9–14 September 1979, Shefayim, Israel.     

Reflex regulation of potassium excretion in the postnatal ontogeny of the dog

In experiments on puppies ageing from 7 days to 8 months, as well as on adult dogs, studies have been made on reflex mechanisms of potassium excretion after injection of 135 mM KCl solution (0.7 ml/kg) to the portal vein. It was found that reflex regulation of potassium extrusion undergoes 3 developmental stages: in puppies up to 1 month potassium excretion is absent; from 1 to 4 months ionuresis is not differentiated, since injection of KCl increases excretion of both K and Na; after 4 months of postnatal life potassium excretion attains its final form. Intravenous injections of pituitrin P reproduce the reactions which were observed in reflex potassium regulation in puppies up to 4 months, this finding indicating possible participation of neurohypophysial hormones in these reactions. In acute experiments it was shown that in puppies of the first month, the liver is not capable of potassium retention. This may be one of the causes of absence of reflex potassium excretion in animals of this age.     

Functional activity of leucocytes in postnatal ontogenesis of dogs]

Studies have been made on motile and phagocytic activity, osmotic fragility of neutrophilic leucocytes, as well as on their glycogen content in dogs of various age groups. Within the first 3 months of postnatal life of animals (especially during the 1st month), functional activity of leucocytes is lower than in adult dogs. With respect to functional activity of leucocytes, 6-month puppies stand closer to adult dogs, although exhibit some differences from the latter.     

Effects of Amphetamine on Protein Synthesis and Energy Metabolism in Mouse Brain: Role of Drug-Induced Hyperthermia

Abstract: Changes in brain protein synthesis activity, and in brain levels of glucose, glycogen, and several high-energy phosphate metabolites, were evaluated under conditions of amphetamine-induced hyperthermia in mice. Protein synthesis showed a striking dependence on rectal temperature ( T _R), falling abruptly at T _R above 40°C. A similar result was obtained following direct heating of the animals. Protein synthesis activity in liver showed the same temperature dependence observed for brain. Increased synthesis of a protein with characteristics of the major mammalian stress protein, hsp 70, was demonstrated in both brain and liver following amphetamine administration. Brain protein synthesis showed significant recovery within 2 h after amphetamine administration whereas that of liver remained below 30% of control activity, suggesting significant temporal and quantitative differences in the response of individual tissues to elevated temperatures. Brain glycogen levels after amphetamine administration were significantly lower under conditions of ambient temperature which resulted in more severe drug-induced hyperthermia but did not correlate as strikingly as protein synthesis with the temperatures of individual animals. Brain glycogen also fell in animals whose temperatures were increased by brief exposure at high ambient temperature. Brain glucose levels did not consistently change with hyperthermia. Slight decreases in high-energy phosphates with increasing T _R were likely the result of fixation artifact. These results demonstrate the fundamental role of hyperthermia in the reduction of protein synthesis in brain and other tissues by amphetamine, and suggest that temperature also constitutes a significant source of variability in the effects of this drug on brain energy metabolism, in particular glycogenolysis.     

Adaptations in skeletal muscle capillarity following changes in oxygen supply and changes in oxygen demands.

The effects of changes in oxygen supply and oxygen demands on fiber cross-sectional areas, capillary densities and capillary to fiber ratios were determined in three skeletal muscles of rat. The muscles examined were the vastus lateralis, soleus, and diaphragm. Reduced oxygen supply was produced by subjecting rats to ambient hypoxia, and increased oxygen demands were produced by subjecting rats to low ambient temperatures or treatment with thyroxin. Capillaries were visualized by injecting fluorescent dyes into the circulation. Muscles were quick frozen at resting lengths to preserve normal fiber geometry and were subsequently sectioned on a cryostat. All of the muscles sampled from animals in the experimental groups had elevated capillary densities. However, capillary to fiber ratios were not increased significantly in any muscle, for any experimental condition. Thus, all of the observed differences in capillarity were due to changes in the intrinsic rate of muscle fiber growth. Further, the relations of capillary density and capillary to fiber ratio to fiber area were the same as those obtained during normal maturation, suggesting that capillary growth is closely linked to the intrinsic rate of fiber growth.     

Experimental replantation of canine forelimbs after 78.5 hours of anoxia

To assess the effect of ischemia on osteocyte survival and longitudinal growth in bone, one forelimb of eight puppies and seven dogs was amputated, perfused with iced Collins solution, maintained at 4 degrees C for 72 hours (78.5 hours total anoxia), and replanted. Five puppies were kept for 1 year to assess bone growth. Undergoing bone labeling on days 1, 8, and 15, the other animals were sacrificed at 22 days to assess osteocyte survival. Osteocytes survived replantation in all dogs and one puppy; most osteocytes died in two puppies. In five long-term puppies, central epiphyseal growth was disturbed, but the peripheral portions maintained nearly normal growth, with almost normal bone length being achieved at 1 year.     

The effect of long-term hyperbarism on pregnant guinea pigs and their progeny

The effect of hyperbarism has been investigated on 1-3-, 4-5- and 8-10-week pregnant rats and their offsprings. It was found that the mortality rate of pregnant rats is two times higher after hyperbaric exposures than in control animals. The animals exhibit the highest sensitivity at a stage of 8-10 weeks. Hyperbaric conditions significantly affect offsprings. Only 53% of newborn puppies were found to be normal, whereas 35% were born dead and 12% revealed various abnormalities. The highest sensitivity was observed during organogenesis (4-5 weeks), the mortality rate during this period reached 70%. The body mass in newborn puppies was significantly lower than in control animals. The most significant retardation in the development was observed in animals which were subjected to the effect of hyperbarism at the 4-5-th week of intrauterine life.     

Influence of aging on Kupffer cell respiratory activity in relation to particle phagocytosis and oxidative stress parameters in mouse liver

The influence of aging on the respiratory activity of stimulated Kupffer cells was investigated in the isolated perfused mouse liver in relation to colloidal carbon phagocytosis, and the content of glutathione (GSH) and protein carbonyls as parameters related to oxidative stress. Livers from aged (22 months) mice exhibited significant 35% and 65% decreases in the carbon uptake and in the carbon-induced O2 consumption compared to young (3 months) animals, respectively, with a concomitant 46% diminution in the carbon-induced O2 consumption/carbon uptake ratio. Hepatic GSH depletion was observed in aged mice compared to young animals, whereas protein oxidation was enhanced. It is concluded that aging leads to an impairment in the functional capacity of Kupffer cells reflected by a substantial reduction in their respiratory burst activity, lessened endocytic capacity and enhanced oxidative stress, that may contribute to increased susceptibility of the liver to noxious challenges.     

Stress-induced thermotolerance of ventilatory motor pattern generation in the locust, Locusta migratoria

Ventilation is a crucial motor activity that provides organisms with an adequate circulation of respiratory gases. For animals that exist in harsh environments, an important goal is to protect ventilation under extreme conditions. Heat shock, anoxia, and cold shock are environmental stresses that have previously been shown to trigger protective responses. We used the locust to examine stress-induced thermotolerance by monitoring the ability of the central nervous system to generate ventilatory motor patterns during a subsequent heat exposure. Preparations from pre-stressed animals had an increased incidence of motor pattern recovery following heat-induced failure, however, prior stress did not alter the characteristics of the ventilatory motor pattern. During constant heat exposure at sub-lethal temperatures, we observed a protective effect of heat shock pre-treatment. Serotonin application had similar effects on motor patterns when compared to prior heat shock. These studies are consistent with previous studies that indicate prior exposure to extreme temperatures and hypoxia can protect neural operation against high temperature stress. They further suggest that the protective mechanism is a time-dependent process best revealed during prolonged exposure to extreme temperatures and is mediated by a neuromodulator such as serotonin.     

Locomotor activity in field captured crepuscular four-striped field mice,Rhabdomys dilectus and nocturnal Namaqua rock mice,Micaelamys namaquensis during a simulated heat wave

Activity of animals is influenced by ambient temperature and increasing temperatures brought about by climate change may impose a heat stress risk. Previous studies investigating the effect of heat waves on activity usually measure animals at different, but constant temperatures, however, rarely are they studied under a natural temperature cycle. General activity, behavioural flexibility and frequency of water drinking counts during a normal day, hot day and a simulated heat wave temperature cycle were studied in the crepuscular four-striped field mouse, Rhabdomys dilectus, and the nocturnal Namaqua rock mouse, Micaelamys namaquensis. Both R. dilectus and M. namaquensis showed typical daily locomotor activity under control conditions. During the heat wave, peak activity times changed for R. dilectus, but both species exhibited higher bouts of activity for the heat wave during the day compared to the control, which was accompanied by an increased amount of time spent drinking water. The increased activity during the heat wave is likely due to enhanced water requirements and potentially a form of behavioural thermoregulation as animals may be uncomfortable and try to move to cooler areas. Thus, in the absence of a typical microclimate, access to water may allow rodents to overcome heat stress from extreme temperatures without having to shift their temporal active times.     

Wheel-running activity and energy metabolism in relation to ambient temperature in mice selected for high wheel-running activity

Interrelationships between ambient temperature, activity, and energy metabolism were explored in mice that had been selectively bred for high spontaneous wheel-running activity and their random-bred controls. Animals were exposed to three different ambient temperatures (10, 20 and 30°C) and wheel-running activity and metabolic rate were measured simultaneously. Wheel-running activity was decreased at low ambient temperatures in all animals and was increased in selected animals compared to controls at 20 and 30°C. Resting metabolic rate (RMR) and daily energy expenditure (DEE) decreased with increasing ambient temperature. RMR did not differ between control and selected mice, but mass-specific DEE was increased in selected mice. The cost of activity (measured as the slope of the relationship between metabolic rate and running speed) was similar at all ambient temperatures and in control and selected mice. Heat generated by running apparently did not substitute for heat necessary for thermoregulation. The overall estimate of running costs was 1.2 kJ/km for control mice and selected mice.