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Perinatal changes in avian muscle: implications from ultrastructure for the development of endothermy.

Endothermic heat production and the capacity to shiver develop soon after hatching in birds, permitting chicks to regulate their body temperature. Physiological studies have not clearly identified the developmental events causing this change in function. Here, we use electron microscopy to examine the development of structures involved in muscle activation, contraction, and metabolism coincident with the development of shivering thermogenesis. A stereological study was used to compare the ultrastructure of chicken iliofibularis before endothermic heat production was present (24 h before hatching) and 120 h later, when the iliofibularis had substantial capacity for shivering. Profound increases were found in the t-tubule system and terminal cisternae, mitochondrial cristae, and lipids. The number of triadic profiles increased 3.8-fold (7.6 +/- 1.31/100 microns 2 to 28.5 +/- 2.90/100 microns 2 fiber area). The surface area of cristae per mitochondrial volume doubled (12.0 +/- 1.50 microns 2/microns 3 to 25.7 +/- 1.84 microns 2/microns 3). Lipid droplets were rare in the iliofibularis of embryos about to hatch, but accounted for 4.4% of the muscle fiber volume in day 4 birds. We suggest that these ultrastructural changes more fully activate the iliofibularis, allow it to produce more heat both from calcium pumping and from contraction, and increase its endurance, thus permitting the muscle to be effective in thermogenesis.

Aging↗

Summer acclimatization in the short-tailed field vole, Microtus agrestis.

We investigated the changes that occurred in basal and noradrenaline-induced metabolic rate, body temperature and body mass in short-tailed field voles, Microtus agrestis, during exposure to naturally increasing photoperiod and ambient temperature. These parameters were first measured in winter-acclimatized voles (n = 8) and then in the same voles which had been allowed to seasonally acclimatize to photoperiod and ambient temperature (6 months later). Noradrenaline induced metabolic rate, basal metabolic rate and non-shivering thermogenesis were significantly higher in winter-acclimatized compared to summer-acclimatized voles. There was a significant positive relationship between basal metabolic rate and noradrenaline-induced metabolic rate. Body mass was significantly higher in summer-acclimatized compared to winter-acclimatized voles. There was a significant positive relationship between body mass and noradrenaline-induced metabolic rate in both winter-acclimatized and summer-acclimatized voles; however, there was no relationship between basal metabolic rate and body mass in either seasonal group of voles. Body temperature after measurements of basal metabolic rate was not significantly different in the seasonal cohorts of voles. However, body temperature was significantly higher in winter-acclimatized compared to summer-acclimatized voles after injection of noradrenaline. Previously we have found that a long photoperiod was not a sufficient stimulus to reduce thermogenic capacity in winter-acclimatized voles during cold exposure, since basal metabolic rate increased to compensate for a reduction in regulatory non-shivering thermogenesis. Here we found that a combination of increased ambient temperature and photoperiod did significantly reduce thermogenic capacity in winter-acclimatized voles. This provided evidence that the two aspects of non-shivering thermogenesis, obligatory and regulatory, are stimulated by different exogenous cues. Summer acclimatization in the short-tailed field vole is manifest as a significant decrease in both basal and noradrenaline-induced metabolic rate, combined with a significant increase in body mass.

Acclimatization↗

Comparative thermoregulatory adaptations of field mice of the genus Apodemus to habitat challenges.

Thermoregulatory abilities, which may play a role in physiological adaptations, were compared between two field mouse species (Apodemus mystacinus and A. hermonensis) from Mount Hermon. While A. hermonensis is common at altitudes above 2100 m, A. mystacinus is common at 1650 m. The following variables were compared in mice acclimated to an ambient temperature of 24 degrees C with a photoperiod of 12L:12D, body temperature during exposure to 4 degrees C for 6 h, O2 consumption and body temperature at various ambient temperature, non-shivering thermogenesis measured as a response to a noradrenaline injection, and the daily rhythm of body temperature. Both species could regulate their body temperature at ambient temperatures between 6 and 34 degrees C. The thermoneutral zone for A. mystacinus lies between 28 and 32 degrees C, while for A. hermonensis a thermoneutral point is noted at 28 degrees C. Both species increased O2 consumption and body temperature as a response to noradrenalin. However, maximal VO2 consumption as an response to noradrenaline and non-shivering thermogenesis capacity were higher in A. mystacinus, even though A. hermonensis is half the size of A. mystacinus. The body temperature rhythm in A. hermonensis has a clear daily pattern, while A. mystacinus can be considered arhythmic. The results suggest that A. hermonensis is adapted to its environment by an increase in resting metabolic rate but also depends on behavioural thermoregulation. A. mystacinus depends more on an increased non-shivering thermogenesis capacity.

Acclimatization↗

Anterior and posterior hypothalamus: effects of independent temperature displacements on heat production in conscious goats.

Three goats were chronically implanted with thermodes to alter the temperatures of the anterior and posterior hypothalamus independently of each other. At an air temperature of +14 degrees C the anterior hypothalamus was cooled with different intensities, while the posterior hypothalamus was simultaneously either warmed (39 degrees C) or cooled (29 degrees C). In both conditions cooling anterior hypothalamus increased heat production. However, the increase was smaller, when the posterior hypothalamus was cooled. The inhibiting effect was most pronounced during the first parts of the periods and diminished with time. Nevertheless, in a separate series of experiments, the effects of posterior hypothalamic cooling were found to persist over periods of 3 h. At an air temperature of +3 degrees C the posterior hypothalamus temperature was altered between 28 and 42 degrees C, while anterior hypothalamus temperature was kept close to its control level. Shivering and heat production decreased with cooling and increased with warming of the posterior hypothalamus. The results suggest that those neurons which reside in the posterior hypothalamus and mediate shivering, are sensitive to temperature. Thermosensitivity of these allegedly integrative neurons affects shivering and heat production in a way inverse to the thermosensitivity of the temperature sensing neurons in the anterior hypothalamus.

Animals↗

The chill sensation in fever.

Seven men were almost totally immersed in water at a neutral temperature (34.5 degrees) and given an intravenous injection of exogenous pyrogen. Five subjects who exhibited fever and visible shivering all reported sensations of chill at the time of shivering. Two subjects who did not shiver reported neutral sensation throughout. The results indicate that reduction of skin temperature is not necessary for the chill sensation in fever. The chill must arise from some central action of pyrogen.

Adult↗

Thermoregulation: what role for UCPs in mammals and birds?

Mammals and birds are endotherms and respond to cold exposure by the means of regulatory thermogenesis, either shivering or non-shivering. In this latter case, waste of cell energy as heat can be achieved by uncoupling of mitochondrial respiration. Uncoupling proteins, which belong to the mitochondrial carrier family, are able to transport protons and thus may assume a thermogenic function. The mammalian UCP1 physiological function is now well understood and gives to the brown adipose tissue the capacity for heat generation. But is it really the case for its more recently discovered isoforms UCP2 and UCP3? Additionally, whereas more and more evidence suggests that non-shivering also exists in birds, is the avian UCP also involved in response to cold exposure? In this review, we consider the latest advances in the field of UCP biology and present putative functions for UCP1 homologues.

Acclimatization↗

Thermosensitivity of the extrahypothalamic brain stem in conscious goats.

In 5 conscious goats, 84 experiments with 881 perfusion periods were performed to explore the brain stem between the rostral medulla and preoptic region for thermo-sensitive structures involved in temperature regulation. The chronically implanted thermodes consisted of 24 or 27 single probes, which were arranged in 8 or 9 rows. The rows of probes were individually perfused with water of 25-46 degrees C to produce discrete temperature stimuli along the brain stem. When the animals were exposed to an air temperature of +4 degrees C, local cooling at various levels of the lower brain stem augmented shivering and increased heat production, which was not regularly followed by a rise in rectal temperature. Ongoing shivering was reduced by local warming of the same sites. In comparison to the effects of hypothalamic thermal stimuli, the magnitude of the lower brain stem responses was reduced. At an air temperature of +30 degrees C local warming of discrete areas of the lower brain stem increased panting and caused a significant rise in respiratory evaporative heat loss. However, panting and shivering were not affected by the same site, and the effective sites of the various animals were not found at corresponding anatomical positions. Thus, thermosensitive sites which are not associated with defined anatomical structures, appear to be dispersed in the lower brain stem of the goat and to interfere with the temperature regulating system.

Animals↗

Expression of neural cell adhesion molecule in dysmyelinating mutants.

The possible role of neural cell adhesion molecule (NCAM) in myelination was studied in the dysmyelinating mouse mutants jimpy and shiverer, by characterizing the expression of the different molecular forms of brain NCAM as a function of age. In jimpy, the expression of NCAM-120 (120,000-Da NCAM) was low and in shiverer both NCAM-120 and NCAM-180 (180,000-Da NCAM) were reduced when compared to controls. In both jimpy and shiverer there was no significant change in the phospholipase C-sensitive NCAM-120. These data further support the possibility that NCAM may be involved in myelination.

Animals↗

Thermoregulatory effects of intraventricularly injected dopamine in the goat.

Dopamine (DA) was injected in the third brain ventricle of goats and the thermoregulatory effects were studied under different ambient conditions. The effects depended on dose, ambient conditions and cannula used. In the cold, there was a drop in body temperature, sometimes accompanied by suppression of shivering and by vasodilatation. Both temperature decrease and suppression of shivering were dose-dependent but there was no relation between magnitude of temperature drop and occurrence of shivering suppression. In a thermoneutral environment, there was either a slight vasoconstriction or hypothermia, occasionally accompanied by induction of panting. In the heat, either hypothermia or hyperthermia was observed. Hypothermia was accompanied by an increase in panting. Hyperthermia only occurred when the animals became excited as a result of the injection of DA. It is concluded that DA acts by stimulating the thermoregulatory pathway from heat sensors to heat loss effectors at a locus similar to that for 5-hydroxytryptamine in the thermoregulation model of Bligh et al. (1971).

Animals↗

Cerebellar soluble lectin and its glycoprotein ligands in the developing brain of control and dysmyelinating mutant mice.

The levels of an endogenous lectin, the cerebellar soluble lectin (CSL) and of its endogenous glycoprotein ligands were studied using immunoblotting and affinoblotting techniques in the forebrain of quaking, shiverer and jimpy dysmyelinating mutant mice and their respective control littermates during the postnatal development. In the controls of the mutant mice, the level of CSL showed an important increase between days 5-18 then a stabilization, although at all ages the level of CSL was reduced (at least 15%) in the control littermate of the shiverer mutant. In the shiverer mutant the developmental pattern is similar to the control but was reduced by 50% as compared to the control. In the jimpy mutant an erratic development of CSL was observed which was with quasi absence of CSL at days 12 and 25. Variation of CSL levels in the quaking brain were also observed. CSL glycoprotein ligands also showed variable developmental profiles with a special persistence with ageing of CSL-binding glycoproteins in the quaking and jimpy mice. Developmental variations were also observed between the different control littermates. These results are discussed in view of developmental roles attributed to CSL and its glycoproteins ligands in cell adhesion mechanism during brain ontogenesis and especially myelination.

Aging↗

Prospective, randomized comparison of the Flotem Iie and Hotline fluid warmers in anesthetized adults.

STUDY OBJECTIVE: To compare the fluid warming capabilities of the Hotline and Flotem IIe devices in surgical patients, and whether warming intravenous (i.v.) fluids with the Hotline device resulted in less hypothermia and less need for other warming methods compared with the Flotem IIe device. STUDY DESIGN: Part 1. Prospective, nonrandomized. Part 2. Prospective, randomized. SETTING: Teaching hospital, tertiary care center. PATIENTS: Part 1. 24 adult patients undergoing elective surgery. Part 2. 49 adult patients scheduled for major elective orthopedic or gynecologic surgery of greater than 2 hours' duration with general anesthesia. INTERVENTIONS: Part 1. Insertion of sterile in-line thermistors along the path of fluids delivered using the Hotline or Flotem device. Part 2. Patients were randomly assigned to receive i.v. fluids via the Hotline (n = 21) or Flotem IIe (n = 18) warmers. Intervention for core hypothermia [lower esophageal temperature (Teso) less than 35.5 degrees C], was with forced air warming. Intervention for postoperative shivering was with meperidine by a nurse who was blinded to the treatment group. MEASUREMENTS: Part 1. Temperature of infused fluids before and after the warmer (T in and T out) and before the fluid entered the patient after insertion of a standard 84 cm extension set having a stopcock for injection of medications (T distal). Part 2. Tympanic (Ttym) was recorded before induction of anesthesia (baseline) and at 15-minute intervals after induction. Teso was recorded at 15-minute intervals after induction. The maximum intraoperative Ttym decline from baseline (delta Ttym max) was calculated. MAIN RESULTS: Part 1. Flow rates were between 1 and 33 ml/min. T out and T distal (mean +/- SEM) of fluids infused through the Hotline device were warmer compared with those infused via the Flotem IIe device (Hotline T out: 35.7 +/- 0.1 degrees C and Hotline T distal: 33.4 +/- 0.2 degrees C vs. Flotem IIe T out: 28.9 +/- 0.2 degrees C and Flotem IIe T distal: 28.3 +/- 0.2 degrees C; p < 0.001 between warmers). Part 2. Maximal decrease in Ttym from preoperative baseline (before intervention) was greater in the Flotem IIe compared with the Hotline group (delta Ttym max = -1.4 +/- 0.1 vs. -0.9 +/- 0.1 degree C, p = 0.01). Five patients in the Flotem IIe group required forced air warming for treatment of hypothermia versus none in the Hotline group (p < 0.01). Postoperatively, five patients in the Flotem IIe group required treatment with meperidine for severe shivering versus one patient in the Hotline group (p < 0.05). CONCLUSIONS: The Hotline device delivered fluids to the patient at consistently warmer temperatures compared with the Flotem IIe device during actual clinical conditions. This was associated with maintenance of near normal core temperatures throughout the procedure in the Hotline group, and a decreased need for interventions such as forced-air warming and treatment for severe shivering.

Adult↗

Facultative and obligatory thermogenesis in young birds: a cautionary note.

A brief overview on thermogenic mechanisms in young precocial birds is given. While shivering thermogenesis is well documented in these birds, evidence for a facultative non-shivering component of heat production, comparable to that found in the brown adipose tissue of mammals, is ambiguous. One reason for this is the confusion between thermoregulatory and obligatory thermogenesis. In particular, the existence of a thermogenic reaction, even a futile one, does not by itself constitute proof of true thermoregulatory non-shivering thermogenesis. More probably, such a reaction is another obligatory component of heat production. Heat increment of feeding and motor activity are classical examples of such mechanisms. Thermogenesis arising from such mechanisms can often be adaptively used by the thermoregulatory systems in young birds, as well as in adults.

Animals↗

Ontogeny of thermoregulatory mechanisms in king penguin chicks (Aptenodytes patagonicus).

The rapid maturation of thermoregulatory mechanisms may be of critical importance for optimising chick growth and survival and parental energy investment under harsh climatic conditions. The ontogeny of thermoregulatory mechanisms was studied in growing king penguin chicks from hatching to the full emancipation observed at 1 month of age in the sub-Antarctic area (Crozet Archipelago). Newly hatched chicks showed small, but significant regulatory thermogenesis (21% rise in heat production assessed by indirect calorimetry), but rapidly became hypothermic. Within a few days, both resting (+32%) and peak (+52%) metabolic rates increased. The first week of life was characterised by a two-fold rise in thermogenic capacity in the cold, while thermal insulation was not improved. During the second and third weeks of age, thermal insulation markedly rose (two-fold drop in thermal conductance) in relation to down growth, while resting heat production was slightly reduced (-13%). Shivering (assessed by electromyography) was visible right after hatching, although its efficiency was limited. Thermogenic efficiency of shivering increased five-fold with age during the first weeks of life, but there was no sign of non-shivering thermogenesis. We conclude that thermal emancipation of king penguin chicks may be primarily determined by improvement of thermal insulation after thermogenic processes have become sufficiently matured. Both insulative and metabolic adaptations are required for the rapid ontogeny of thermoregulation and thermal emancipation in growing king penguin chicks.

Animals↗

Influence of early postnatal cold exposure on myofiber maturation in pig skeletal muscle.

Early after birth, piglets rely almost exclusively on muscular shivering thermogenesis to produce heat in the cold and this can possibly modulate skeletal muscle development. An experiment involving 10 individually housed piglets was conducted to determine the influence of cold (24-15 degrees C, D5C group) vs. thermoneutrality (34-30 degrees C, D5TN group) between birth and 5 days on myosin heavy chain (MyHC) polymorphism and metabolic characteristics of longissimus lumborum (LL) and rhomboideus (RH) muscles. Five additional piglets were sacrificed at birth. Piglets exposed to cold received 43% more artificial milk on a liveweight basis in order to achieve similar growth rates. D5C piglets produced 93% more heat and exhibited intense shivering during the whole experiment. Contractile and metabolic characteristics of muscles were determined by immunocytochemistry, electrophoresis and enzyme activities. At least eight MyHC isoforms were detected, including atypical expressions of the alpha-cardiac and extraocular isoforms. Dramatic changes in MyHC composition, myofiber cross-sectional area (CSA) and energy metabolism occurred between birth and 5 days. Cold exposure did not affect either the total number of fibers or the CSA, but it did influence muscle maturation. In particular, it increased the expression of alpha-cardiac and type I MyHC, and decreased that of fetal MyHC, confirming an acceleration in the rate of postnatal maturation. An increase in oxidative enzyme activities was observed in both muscles in the cold, whereas the activity of a glycolytic enzyme, lactate dehydrogenase, remained unchanged. Cold exposure also induced an increase in T3 plasma levels. The extent to which these changes are the result of sustained shivering or are due to the action of hormonal factors, such as thyroid hormones, are discussed.

Age Factors↗

Increased proton conductance pathway in brown adipose tissue mitochondria of rats exhibiting diet-induced thermogenesis.

It has recently been demonstrated that in rats induced to overeat by being fed a varied and palatable diet (the 'cafeteria diet') there is a marked increase in heat production which serves to reduce, or prevent, the development of obesity. This diet-induced thermogenesis is associated with increases in sympathetic activity, and with changes in brown adipose tissue. Following cafeteria feeding, brown adipose tissue hypertrophies and and exhibits increased lipolysis and an apparently greater thermogenesis in response to noradrenaline. These metabolic changes resemble those seen during non-shivering thermogenesis in cold-adapted rats, and it was proposed that non-shivering thermogenesis and diet-induced thermogenesis have a similar metabolic origin which depends on the unique capacity of brown adipose tissue for thermogenesis. During non-shivering thermogenesis heat is produced in brown adipose tissue through a proton conductance pathway across the inner mitochondrial membrane that dissipates the proton gradient generated by respiration. The activity of the proton conductance pathway can be modulated by purine nucleotides, and changes in the pathway seem to be related to the level of purine nucleotide binding to brown adipose tissue mitochondria. We now report results which indicate that the proton conductance pathway is augmented in cafeteria-fed rats, and suggest that it operates to dissipate their excess energy intake through diet-induced thermogenesis

Adipose Tissue↗

Sodium channel density in hypomyelinated brain increased by myelin basic protein gene deletion.

Trophic control over the expression and membrane distribution of voltage-dependent ion channels is one of the principal organizing events underlying the maturation of excitable cells. The myelin sheath is a major structural determinant of regional ion channel topography in central axons, but the exact molecular signals that mediate local interactions between the oligodendrocyte and axolemma are not known. We have found that large caliber fibre pathways in the brain of the mutant mouse shiverer (shi, gene on chromosome 18), whose developmental fate of myelination is averted by deletion of five exons in the myelin basic protein gene, have a striking excess of sodium channels. As cytoplasmic membranes of shiverer oligodendroglia still adhere to axons, the evidence indicates that myelin basic protein or a myelin basic protein-dependent glial transmembrane signal associated with compact myelin formation, rather than a simple glial-axon contact inhibition or an intrinsic genetic program of neuronal differentiation, could be critical in downregulating sodium channel density in axons. Here we use the shiverer mutant to show that mature central nervous system projection neurons with large caliber unmyelinated fibres sustain functional excitability by increasing sodium channel density. This axon plasticity, triggered by the absence of a single glial protein, contributes to the unexpectedly mild degree of neurological impairment in the mutant brain without myelin, and may be a potentially inducible mechanism determining the recovery of function from dysmyelinating disease.

Animals↗

[Postoperative routine use of physostigmine on vigilance, cardiovascular parameters and need of analgesics].

OBJECTIVE: A central anticholinergic syndrome (CAS) can be related to the majority of anesthetic agents, but is often not recognized as such. Thus, most anesthesiologists seem to miss the occurrence of an anticholinergic syndrome especially when agitation and/or restlessness are the major symptoms. Therefore, the following study was undertaken to test the hypothesis that routine administration of the anticholinergic agent physostigmin is of benefit for patients in regard to vigilance, the cardiovascular system and the need of analgesics easing the time in the post anesthesia care unit (PACU). METHODS: After approval by the local ethics committee and written informed consent, 100 patients undergoing a cholecystectomy or a struma resection, were given either physostigmin (n = 51) or saline 0.9 % (n = 49) in a randomized fashion. The study was conceived to block a possible isoflurane-N2O/O2 (opioid-based plus relaxant) induced central anticholinergic syndrome and to evaluate the effects on the cardiovascular system on vigilance and on postoperative analgesic demand. Following parameters were measured: systolic and diastolic blood pressure, heart rate, respiratory rate, and arterial blood gases. In addition, vigilance was determined and typical anticholinergic symptoms (disorientation, slurred speech, agitation, nausea, emesis, cardiac arrhythmia and muscle shivering) were determined 10, 20, 40 and 60 minutes following the intravenous injection of physostigmin. Also, the need for the postoperative analgesic pethidine was evaluated among the two groups. RESULTS: Except for a significant reduction in the need of analgesics, a reduced diastolic pressure and heart rate and a lower incidence of muscle shivering there was no difference among the two groups. One major side effect following the use of physostigmin was the higher incidence of nausea in the im mediate minutes following injection. This effect may be due to the rapid injection of the anticholinergic compound. Otherwise there were no detrimental effects of physostigmin in patients. CONCLUSION: From the results it can be concluded that routine administration of an anticholinergic agent results in a short term beneficial effect in regard to vigilance, a lesser incidence of muscle shivering and a lesser demand for analgesics. However, because of the low incidence of a classical central anticholinergic syndrome, routine physostigmine is only indicated when agitation is diagnosed.

Adult↗

Influence of thyrotropin-releasing hormone administration at birth on thermoregulation in lambs delivered by cesarean.

OBJECTIVE: We examined the hypothesis that exogenous stimulation with thyrotropin-releasing hormone immediately before umbilical cord clamping can improve thermoregulation in near-term lambs delivered by cesarean. STUDY DESIGN: Twin lambs were injected with either saline solution alone (control, n = 12) or thyrotropin-releasing hormone in saline solution (n = 16) and were immediately placed in a warm (30 degrees C; n = 14) or cool (15 degrees C; n = 14) ambient temperature. In vivo measurements of temperature control (colonic temperature, oxygen consumption, and incidence of shivering) were then performed during the first 6 hours after birth, in conjunction with plasma thyroid hormone measurements. Brown adipose tissue was then sampled for measurement of uncoupling protein 1 abundance. RESULTS: Plasma triiodothyronine concentrations were significantly higher in lambs treated with thyrotropin-releasing hormone than in control lambs between 3 and 6 hours after birth, as were plasma thyroxine concentrations 1 and 5 hours after birth. Delivery temperature had no effect on plasma thyroid hormone concentrations. At 6 hours after birth the abundance of uncoupling protein 1 was higher in lambs treated with thyrotropin-releasing hormone than in control lambs. Lambs treated with thyrotropin-releasing hormone exhibited a lower incidence of shivering than did control lambs between 5 and 6 hours after birth, and an effect of ambient temperature on the incidence of shivering was observed only in the control group. From 3 to 6 hours after birth colonic temperature was significantly higher in cool-delivered lambs treated with thyrotropin-releasing hormone than in the control group. Oxygen consumption was higher in cool-delivered lambs than warm-delivered lambs, but this was not influenced by thyrotropin-releasing hormone. Irrespective of delivery temperature, lambs treated with thyrotropin-releasing hormone possessed more pericardial adipose tissue and hepatic glycogen than did control lambs. CONCLUSION: Thyrotropin-releasing hormone treatment stimulated thyroid hormone secretion in the neonatal lamb and improved thermoregulation during the first 6 hours after birth in near-term lambs delivered by cesarean under cool conditions.

Adipose Tissue, Brown↗