SEARCH · Search PubMed

Results for “SHIVERING”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 937 records · Page 52Linked to original sources

PubMed1998

Endogenous myelin basic protein inactivates the high avidity T cell repertoire.

To study the contribution of endogenous myelin basic protein (MBP) to the positive and/or negative selection of the MBP-specific T cell repertoire, we studied the T cell response to MBP in MBP-deficient shiverer and MBP-expressing congenic C3H mice. Immunization with MBP induced a vigorous T cell response in shiverer mice directed against a single I-Ak- restricted immunodominant determinant, the core of which is peptide MBP:79-87 (DENPVVHFF). Injection of this peptide induced a high avidity T cell repertoire in shiverer mice that primarily consisted of clones capable of recognizing the native MBP protein in addition to the peptide itself. These data show that endogenous MBP is not required for the positive selection of an MBP-specific T cell repertoire. C3H mice, in contrast, were selectively unresponsive to the MBP protein and injection of MBP:79-87 peptide induced a low avidity repertoire that could be stimulated only by the peptide, not by the protein. Therefore, endogenous MBP induced profound inactivation of high avidity clones specific for the immunodominant determinant making that determinant appear cryptic.

Animals↗

PubMed2005

Alteration of brain type N-glycans in neurological mutant mouse brain.

We have previously detected two brain-specific and development-dependent N-glycans [H. Shimizu, K. Ochiai, K. Ikenaka, K. Mikoshiba, and S. Hase (1993) J. Biochem. 114, 334-338]. In the present study we attempted to analyze specific N-glycans detected in neurological mutant mice. N-glycans in cerebrum and cerebellum obtained from 3-week-old neurological mutant mice (jimpy, staggerer, and shiverer) were compared with those obtained from normal mice. N-glycans liberated from the cerebrum and cerebellum by hydrazinolysis-N-acetylation were pyridylaminated, and pyridylamino derivatives of N-glycans thus obtained were separated into neutral and five acidic fractions by anion exchange chromatography. PA-N-glycans in each fraction were compared with those obtained from normal mice by reversed-phase HPLC, and the following results were obtained. The ratio of the two brain-type N-glycans, Manalpha1-3(GlcNAcbeta1-2Manalpha1-6)(GlcNAcbeta1-4)Manbeta1-4GlcNAcbeta1-4(Fucalpha1-6)GlcNAc (BA-1) to GlcNAcbetaManalpha1-3(GlcNAcbeta1-2Manalpha1-6)(GlcNAcbeta1-4)Manbeta1-4GlcNAcbeta1-4(Fuca1-6)GlcNAc (BA-2), was higher in staggerer mice than other mutant mice and normal mice. Sia-Gal-BA-2, triantennary N-glycans, and bisected biantennary N-glycans were found in the cerebellum of shiverer and staggerer mice but not in normal or jimpy mice. High-mannose type N-glycans were not altered in mutant mice brains. The amounts of disialylbiantennary N-glycans and disialylfucosylbiantennary N-glycans were lower in jimpy mouse cerebellum than in normal mouse cerebellum, but were higher in shiverer mouse. Some alterations of N-glycans specific to mutations were successfully identified, suggesting that expression of component(s) of the N-glycan biosynthetic pathway was specifically affected in neurological mutations.

Animals↗

PubMed1994

The fate of Schwann cells in peripheral nerve allografts.

The phenotype of Schwann cells, whether of host or donor origin, in nerve allografts has been a source of debate. The origin of Schwann cells in peripheral nerve allografts under conditions of no, temporary or continuous immunosuppression was assessed by immunohistochemistry. We hypothesized that host-derived Schwann cells would replace rejected foreign donor Schwann cells after withdrawal of immunosuppression. A murine model of nerve transplantation to normal (wild-type) hosts from donor Shiverer mice, a mutant whose Schwann cells are deficient in myelin basic protein, was used and antibody reactivity against myelin basic protein was employed to ascertain the identity of Schwann cells in the nerve allograft. Without immunosuppression, donor Shiverer Schwann cells were rejected and the nerve graft morphology was restored by host-derived Schwann cells. With continuous immunosuppression, donor Shiverer Schwann cells persisted in the graft segment, associated with a chronic rejection phenomenon. The latter allowed migration of host-derived Schwann cells, over time, into the graft segment in approximately half the cases. After withdrawal of finite (6 weeks) immunosuppression, a rejection response eliminated donor Schwann cells. Replacement by host Schwann cells ensured as was hypothesized.

Animals↗

PubMed2005

No difference in emergence time and early cognitive function between sevoflurane-fentanyl and propofol-remifentanil in patients undergoing craniotomy for supratentorial intracranial surgery.

Balanced anesthesia with sevoflurane-fentanyl has been widely accepted as anesthetic management for neurosurgery. Propofol-remifentanil regimen has been successfully used in various surgical settings, but a comprehensive comparison of sevoflurane-fentanyl and propofol-remifentanil anesthesia in patients undergoing craniotomy for supratentorial intracranial surgery has not yet been done. The aim of this prospective, randomized, open-label clinical trial was to compare clinical properties of sevoflurane-fentanyl with propofol-remifentanil anesthesia in patients undergoing supratentorial intracranial surgery. The primary endpoint was to compare early postoperative recovery and cognitive functions within the two groups; we also evaluated hemodynamic events, vomiting, shivering, and pain. One hundred twenty patients (64 males; age 15-75 years) were randomized to either total intravenous anesthesia (group T) or sevoflurane anesthesia (group S). Emergence and extubation times and cognitive function (Short Orientation Memory Concentration Test [SOMCT]) were compared in the two groups. Brain swelling, incidence of hypotensive and hypertensive episodes, postoperative vomiting, shivering, and pain were also analyzed. The mean emergence time (12.2 +/- 4.9 minutes for group S versus 12.3 +/- 6.1 minutes for group T; P = 0.92) and extubation time (18.2 +/- 2.3 minutes for group S versus 18.3 +/- 2.1 minutes for group T; P = 0.80) were similar in the two groups. Average SOMCT scores, both 15 minutes after extubation (25.6 +/- 4.9 in group S versus 23.9 +/- 7.5 in group T; P = 0.14) and 45 minutes after extubation (27.3 +/- 2.2 in group S versus 26.0 +/- 5.1 in group T; P = 0.07) were also comparable. Brain swelling was present in seven and five patients in groups S and T, respectively (P = 0.76). Hypotension was present in 12% (group S) and 28% (group T) of patients (P = 0.02). Hypertension was present in 17% of patients in group S and 40% of patients in group T (P = 0.0046). Shivering was present in 18% and 25% of patients in groups T and S (P = 0.37). Our study demonstrates that there is no patient benefit of using total intravenous anesthesia with an ultra-short-acting opioid over the conventional balanced volatile technique in terms of recovery and cognitive functions.

Adolescent↗

PubMed2000

A double-blind placebo controlled randomised trial of misoprostol and oxytocin in the management of the third stage of labour.

OBJECTIVE: To compare oral misoprostol 400 microg with intramuscular oxytocin 10 IU in the routine management of the third stage. DESIGN: Double-blind placebo controlled trial. SETTING: Main referral hospital and its associated polyclinics in Accra, Ghana. POPULATION: Four hundred and one low risk women, in the second stage of labour with anticipated vaginal delivery, who entered labour spontaneously. METHODS: After delivery of the anterior shoulder of the baby, the women were randomised to receive either: 1. misoprostol 400 microg powder in water orally and 1 mL normal saline intramuscular injection (placebo); or 2. powdered cellulose in water orally (placebo) and 1 mL oxytocin 10 IU intramuscular injection. MAIN OUTCOME MEASURES: Change in haemoglobin concentration from before delivery to 12 hours postpartum. Secondary outcomes included need for additional oxytocics, blood loss > 500 mL and > 1,000 mL, operative intervention for postpartum haemorrhage, and side effects, including nausea, vomiting, diarrhoea, shivering and elevated temperature. RESULTS: Demographic characteristics were similar. There was no significant difference in change in haemoglobin concentration between the two groups (0.60 g/dL for misoprostol and 0.55 g/dL for oxytocin; relative difference 9.6%; 95% CI 20.5-39.6%; P = 0.54). There were no significant differences in secondary outcomes with the exception of shivering, which occurred more frequently in the misoprostol group (22.2% vs 5.7%; relative risk 4.73; 95% CI 2.31-9.68; P < 0.0001). CONCLUSIONS: In low risk women oral misoprostol appears to be as effective in minimising blood loss in the third stage of labour as intramuscular oxytocin. Shivering was noted more frequently with misoprostol use, but no other side effects were noted. Misoprostol has great potential for use in the third stage of labour especially in developing countries.

Administration, Oral↗

PubMed1986

Expression of myelin proteolipid protein and basic protein in normal and dysmyelinating mutant mice.

Expression of myelin proteins was studied in the brains of 21-day-old normal mice and three dysmyelinating mutants-jimpy, quaking, and shiverer. Total brain polyribosomes and poly(A)+ mRNA were translated in two cell-free systems and the levels of synthesis of the myelin basic proteins (MBPs) and proteolipid protein (PLP) were determined. Synthesis of the MBPs in quaking homozygotes was at or above normal levels but PLP synthesis was significantly reduced to approximately 15% of control values, indicating independent effects on the expression of these proteins in this mutant. Immunoblot analysis of 21-day-old quaking brain homogenates showed a reduction in the steady-state levels of MBPs and PLP, suggesting a failure of newly synthesized MBPs to be incorporated into a stable membrane structure such as myelin. In the shiverer mutant very little synthesis of MBPs was observed, whereas greater synthesis of PLP occurred (approximately 50% of control). Almost no MBP, and low levels of PLP, were detected in the immunoblots, suggesting the possibility of a partial failure of PLP to be assembled into myelin in shiverer. In the jimpy mutant, low levels of MBP synthesis were observed in vitro (approximately 26% of controls) and very little synthesis of PLP was evident. The immunoblots of 21-day jimpy brain homogenates revealed no appreciable steady-state levels of PLP or MBP, again indicating that most newly synthesized MBPs were not incorporated into a stable membrane structure in this mutant. In sum, the data show that in the three cases examined, the mutation appears to affect the expression of the MBPs and PLP independently. Furthermore, regardless of their absolute levels of synthesis these proteins may or may not be assembled into myelin.

Animals↗

PubMed1987

Inefficient transcription of the myelin basic protein gene possibly causes hypomyelination in myelin-deficient mutant mice.

A hereditary dysmyelination mutation, named myelin deficient (mld), is considered to be allelic to shiverer, a deletion mutation of the myelin basic protein (MBP) gene. The present study showed that MBP expression is greatly reduced in mld, but that it is still detectable. Northern blot analysis revealed that the pronounced decrease in the MBP level in mld resulted from a reduced mRNA level and was not caused by deletion of a large portion of the MBP gene as in shiverer. Southern blot studies with BamHI-digested chromosomal DNA suggested some part of the MBP gene, at least the 5'-portion, was duplicated in mld. These results indicated that the mld and shiverer mutations were different from each other, even though genetic allelism between the two was reconfirmed. We also examined the developmental pattern of the gene expression of MBP and that of another protein, myelin proteolipid protein (PLP), specifically expressed in the oligodendrocyte, in mld by RNA dot blot study. The mRNA level of MBP in mld was greatly reduced during the active myelination stages, gradually increasing and remaining constant in the later stages. The PLP-mRNA content in mld was almost normal (60-80% that of control) at any stage of development. All these findings imply that the primary defect in mld is due to reduced transcriptional activity of the MBP gene.

Alleles↗

PubMed1992

Morphometric analysis of normal, mutant, and transgenic CNS: correlation of myelin basic protein expression to myelinogenesis.

The neurological mutant mice shiverer (shi) and myelin deficient (shimld) lack a functional gene for the myelin basic proteins (MBP), have virtually no myelin in their CNS, shiver, seize, and die early. Mutant mice homozygous for an MBP transgene have MBP mRNA and MBP in net amounts approximately 25% of normal, have compact myelin, do not shiver or seize, and live normal life spans. We bred mice with various combinations of the normal, transgenic, shi, and shimld genes to produce mice that expressed MBP mRNA at levels of 0, 5, 12.5, 17.5, 50, 62.5, and 100% of normal. The CNS of these mice were analyzed for MBP content, tissue localization of MBP, degree of myelination, axon size, and myelin thickness. MBP protein content correlated with predicted MBP gene expression. Immunocytochemical staining localized MBP to white matter in normal and transgenic shi mice with an intensity of staining comparable to the degree of MBP gene expression. An increase in the percentage of myelinated axons and the thickness of myelin correlated with increased gene expression up to 50% of normal. The percentage of myelinated axons and myelin thickness remained constant at expression levels greater than 50%. The presence of axons loosely wrapped with oligodendrocytic membrane in mice expressing lower amounts of MBP mRNA and protein suggested that the oligodendroglia produced sufficient MBP to elicit axon wrapping but not enough to form compact myelin. Mean axon circumference of myelinated axons was greater than axon circumference of unmyelinated axons at each level of gene expression, further evidence that oligodendroglial cells preferentially myelinate axons of larger caliber.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1984

Modes of thermal protection in newborn muskoxen (Ovibos moschatus).

The muskoxen (Ovibos moschatus), a native of Greenland and the Canadian North West Territories, give birth in late April, and the newborn calves are known to tolerate an ambient temperature (Ta) of -35 degrees C. At birth the calves weigh about 8 kg, increasing in weight with 0.6 kg . day-1 for the first 30 days. With a deep body temperature (DBT) of 39.5 degrees C (range 37.7-41.3 degrees C) the newborn calves are consequently able to maintain a thermogradient of at least 70 degrees C between body core and the environment. The calves use primarily two modes of thermal protection: High metabolic heat production and prime fur insulation. Metabolic rate was about 3.5 W . kg-1 at thermoneutrality in calves aged from 8 h to 7 days. Lower critical temperature at this age was about -7 degrees C and a drop in Ta to -30 degrees C increased metabolism to about 5.3 W . kg-1. Upper critical temperature at age 4-7 days is as low as 20 degrees C, while it in calves aged only 18-24 h appears to be even lower. The calves possess great amounts of brown adipose tissue (BAT) at birth. Mitochondria from the BAT deposits were isolated and found to be in an extremely loose-coupled state with a great capacity for thermogenesis. Skeletal muscle contained very few mitochondria and is hardly employed in aerobic non-shivering thermogenesis. Calves shiver visibly while drying just after birth, but are normally not seen shivering thereafter. The conductance value for the dry pelt of newborn calves averaged 3.2 W . m-2 . 0 degrees C-1 (n = 4). Wetting of the pelt with ice-water at a Ta of 3 degrees C increased conductance to 8.8 W . m-2 . 0 degrees C-1. The conductance of the pelt was also influenced by wind, being 10 W . m-2 . C-1 at a wind-speed of 10 m . sec-1. The legs of the newborn calves are heavily furred and countercurrent circulation is not present, subcutaneous temperature just above the hooves being +29.8 degrees C at Ta of -24 degrees C as compared to 37.5 degrees C on the back. The newborn calves could cope with a Ta of -30 degrees C without apparent problems under experimental conditions, but they suffered hypothermia when exposed to a Ta of -33 degrees C in combination with wind of 10 m . sec-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Physiological↗

PubMed1987

Appropriate and inappropriate hypothalamic cold thermosensitivity in Willow ptarmigan.

Hypothalamic thermosensitivity has been investigated in conscious Willow Ptarmigan (Lagopus lagopus lagopus) provided with chronically implanted hypothalamic perfusion thermodes. The birds were exposed to either cold (Ta - 10 degrees C) or warm (Ta + 25 degrees C) ambient conditions while hypothalamic temperature (Thy) was clamped for periods of 20 min at different set levels between 28 degrees C and 43 degrees C. The responses of the animals to hypothalamic thermal stimulation were classified by comparing them with those normally found in mammals. At Ta - 10 degrees C hypothalamic heating inhibited ongoing shivering, causing a fall in body-core temperature (Tc) (appropriate mammalian-like response). Strong levels of hypothalamic cooling (Thy less than 34.0 degrees C) also caused a fall in Tc due to inhibition of shivering (inappropriate mammalian-like response). However, weaker levels of hypothalamic cooling (Thy 34-36 degrees C), facilitated ongoing shivering, resulting in small increases in Tc (appropriate mammalian-like response). At Ta + 25 degrees C hypothalamic heating facilitated ongoing panting while weak (Thy 38 degrees C) levels of hypothalamic cooling inhibited ongoing panting (both mammalian-like responses). The observation of a weak mammalian-like cold hypothalamic thermosensitivity in Willow Ptarmigan indicates that these birds possess some specific cold thermosensors in the hypothalamic region. This finding suggests that hypothalamic temperature dependence in birds and mammals is fundamentally similar.

Animals↗

PubMed1983

Seasonal acclimatization in American goldfinches: the role of the pectoralis muscle.

The present study attempts to assess whether the marked seasonal changes in the capacity for shivering thermogenesis in American goldfinches (Carduelis tristis) involve adjustments of metabolic pathways of the pectoralis muscles similar to those observed in mammalian muscle in response to endurance training, i.e., changes favoring increased reliance on fatty acid oxidation and decreased utilization of carbohydrate reserves. Analysis of seasonal changes in enzyme profile of the pectoralis muscle revealed that winter-acclimatized birds have significantly greater (P less than 0.05) activities of phosphorylase, phosphofructokinase, and beta-hydroxy-acyl-CoA dehydrogenase than do birds in other seasons. The activities of citrate synthase and hexokinase do not vary seasonally. These results differ fundamentally from the pattern of changes in enzyme activities associated with endurance adaptation in mammals. Furthermore no seasonal changes were observed in capacities for the oxidation of fatty acids (palmitate and linoleate) or pyruvate in either crude homogenates or isolated mitochondria of goldfinch pectoralis muscles. The oxidation of pyruvate by isolated pectoralis muscle mitochondria was inhibited (greater than 90%) by the oxidation of palmitoyl carnitine at palmitoyl carnitine concentrations as low as 50 microM. These data agree with physiological observations indicating little use of glucose by this tissue during steady-state shivering. However, the extent of this inhibition does not vary seasonally. Therefore the present study fails to document any significant seasonal change in the catabolic pathways of the pectoralis muscle that would link observed seasonal changes in capacity for shivering thermogenesis with a shift in the balance of substrate use by this tissue.

3-Hydroxyacyl CoA Dehydrogenases↗

PubMed1977

Hypothalamic thermoregulatory pathways in the rat.

The cutaneous blood flow (mbl), rate of oxygen consumption (Vo2), rectal (Tre) and cutaneous (Tsk) temperatures, and shivering activity were measured in unanthetized male rats during a 2-h exposure to 26, 33, or 5 degrees C 2 wk after selective bilateral hypothalamic microknife cuts. Animals with preoptic-anterior hypothalamic (PO/AH) junction cuts 1.5 or 3.0 mm lateral to the midline, as well as parasagittal cuts which separated connections between the PO/AH and medial forebrain bundle exhibited a higher mbl at 26 degrees C than did sham-operated rats. At 5 degrees C the extended (3.0 mm) PO/AH cuts as well as the parasagittal cuts prevented cutaneous vasoconstriction but had no effect on shivering activity; hence Tre was not maintained. None of the cuts demonstrably impaired thermoregulation in the 33 degrees C environment. These results suggest that different sites in the hypothalamus may separately control cold-induced skin vasoconstriction and shivering activity, as well as heat-induced skin vasodilation. It would seem therefore that the integrity of the PO/AH is indispensable in rats for cold-induced cutaneous vasoconstriction but not for cold thermogenesis, and also not for heat-induced cutaneous vasodilation.

Animals↗

PubMed1993

Ventilatory and metabolic responses to cold and CO2 in intact and carotid body-denervated awake rats.

We investigated in conscious rats the characteristics and modes of action of CO2 on thermoregulation and ventilatory control during cold stress. In a group of 10 rats studied intact and after carotid body denervation, measurements of metabolic rate (VO2), ventilation (V), shivering, and colonic temperature (Tc) were made at controlled ambient temperatures (Ta) of 25, 20, 15, 10, and 5 degrees C. Animals were exposed on different days to 1) normoxia, 2) normoxia and 4% CO2, 3) 12% hypoxia, or 4) 10.8% hypoxia and 4% CO2. The following results were obtained. 1) During CO2 exposure in normoxia or hypoxia, VO2 is increased at Ta of 25 degrees C and decreased for lower Ta. These effects are partly mediated by carotid body afferents. 2) Shivering and nonshivering thermogenesis and therefore Tc regulation are affected by CO2 exposure as shown by relationships between VO2-Tc and VO2-shivering intensity. 3) V is controlled by PO2 and PCO2 directly through their peripheral and central actions but also indirectly through their effects on VO2. Our conclusions are as follows. 1) Control of Tc is markedly dependent on PCO2 level. Carotid body afferents play a role, but direct central effects acting on the different sources of thermogenesis and possibly on thermolysis are most prominent. 2) As far as control of V is concerned, during hypercapnia in normoxia or hypoxia, several analogies may be formed between exposure to cold and muscular exercise, both of which increase VO2 and V, suggesting common integrative mechanisms at the central nervous system level.

Animals↗

PubMed1995

Human temperature regulation during subanesthetic levels of nitrous oxide-induced narcosis.

The present study investigated whether nitrous oxide (N2O) attenuates shivering thermogenesis during cold water immersion in a dose-dependent manner. Seven male subjects were immersed to the neck for 60 min in 20 degrees C water on five separate occasions while breathing either air (AIR) or a normoxic mixture of 10, 15, 20, or 25% N2O balanced with N2. All N2O concentrations investigated caused a significant (P < 0.02) reduction in shivering thermogenesis compared with AIR. Despite similar heat flux from the skin, the relative changes in esophageal temperature from resting preimmersion levels were significantly greater (P < 0.05) during the N2O trials compared with AIR, with no significant difference among the N2O conditions. A dose-dependent trend in the perception of thermal comfort was observed for the N2O conditions. It is concluded that shivering thermogenesis, and thus thermal balance, is affected to the same degree for the range of inspired N2O concentrations investigated, with no discernable dose-dependent effect.

Adult↗

PubMed1996

Wet-cold exposure and hypothermia: thermal and metabolic responses to prolonged exercise in rain.

Simulated conditions of hiking in rain, wind, and cold, without protective rainwear, were used to investigate wet-cold hypothermia in 18 male subjects. Thermal, metabolic, and motor responses were monitored during an attempted 5-h walk (5.1 km/h) at 5 degrees C, with continuous exposure to rain (7.4 cm/h) and wind (8.0 km/h) over the final 4 h. The majority of subjects (11) could not complete the protocol because of intolerance of wet-cold conditions during the last 2 h. Therefore, data from 5 subjects who completed the protocol in rain and control conditions were used to describe the general pattern of response. During the 1st h of walking, core temperature rose 1 degree C to 38.1 degrees C. The subsequent 2 h of rain caused substantial cold stress, indicated by a 40% increase in heat production due to shivering and significant loss of strength and manual dexterity. However, core temperature only decreased to 37.1 degrees C, merely eliminating the initial exercise hyperthermia. Over the last 2 h of rain, core temperature remained relatively stable at 36.8 degrees C, decreasing slightly to 36.4 degrees C by 5 h. Two other subjects developed significant hypothermia (35 degrees C). One demonstrated fatigue of shivering after 2.5 h of rain, confirming the exhaustion hypothesis of wet-cold hypothermia. The older cooled rapidly when he failed to maintain the walking pace. We conclude that if a person can tolerate the intense discomfort of prolonged wet-cold exposure, he or she has the potential to resist significant core hypothermia for at least 4 h of walking under the conditions of this experiment. Exceptions to this generalization occur, making exposure of < 4 h a hypothermia risk for some individuals. Exposures > 4 h would involve increasing probability of rapid decline into hypothermia, associated with exhaustion of shivering and exercise heat production.

Adult↗

PubMed1998

Cold-induced thermoregulation and biological aging.

Aging is associated with diminished cold-induced thermoregulation (CIT). The mechanisms accounting for this phenomenon have yet to be clearly elucidated but most likely reflect a combination of increased heat loss and decreased metabolic heat production. The inability of the aged subject to reduce heat loss during cold exposure is associated with diminished reactive tone of the cutaneous vasculature and, to a lesser degree, alterations in the insulative properties of body fat. Cold-induced metabolic heat production via skeletal muscle shivering thermogenesis and brown adipose tissue nonshivering thermogenesis appears to decline with age. Few investigations have directly linked diminished skeletal muscle shivering thermogenesis with the age-related reduction in cold-induced thermoregulatory capacity. Rather, age-related declines in skeletal muscle mass and metabolic activity are cited as evidence for decreased heat production via shivering. Reduced mass, GDP binding to brown fat mitochondria, and uncoupling protein (UCP) levels are cited as evidence for attenuated brown adipose tissue cold-induced nonshivering thermogenic capacity during aging. The age-related reduction in brown fat nonshivering thermogenic capacity most likely reflects altered cellular signal transduction rather than changes in neural and hormonal signaling. The discussion in this review focuses on how alterations in CIT during the life span may offer insight into possible mechanisms of biological aging. Although the preponderance of evidence presented here demonstrates that CIT declines with chronological time, the mechanism reflecting this attenuated function remains to be elucidated. The inability to draw definitive conclusions regarding biological aging and CIT reflects the lack of a clear definition of aging. It is unlikely that the mechanisms accounting for the decline in cold-induced thermoregulation during aging will be determined until biological aging is more precisely defined.

Aging↗

PubMed1996

Effect of beta 3-adrenergic agonist (Zeneca D7114) on thermoregulation in near-term lambs delivered by cesarean section.

We investigated the effect of a beta 3-adrenergic agonist, Zeneca D7114, on thermoregulation in near-term lambs delivered by cesarean section. Lambs were delivered into a cool ambient temperature of 15 degrees C, and between 60 and 80 min of life were given an oral dose of Zeneca D7114 (10 mg.kg body weight-1) dissolved in 20 mL of milk, or milk alone. During the first 0.5 h of life colonic temperature decreased in all lambs, and then increased to plateau levels (39.6-40.4 degrees C) after 120-150 min of life, in 19 out of 23 lambs studied. In the remaining lambs, colonic temperature failed to return to normothermic values, plateauing at 34.3 degrees C. All control lambs were observed to shiver throughout the study, but after Zeneca D7114 treatment 7 out of 10 normothermic lambs stopped shivering, and plateau colonic temperature was 0.8 degree C higher. Hypothermic beta 3-agonist-treated lambs had significantly lower rates of heat production, breathing frequency, and plasma triiodothyronine and cortisol concentrations than normothermic lambs. the level of GDP binding and norepinephrine content of brown adipose tissue (BAT) sampled from hypothermic beta 3-agonist-treated lambs was significantly lower than in normothermic lambs. There was no difference in GDP binding in BAT between control and Zeneca D7114-treated groups, but the Hb content was higher in the latter group. It is concluded that administration of Zeneca D7114 to euthyroid lambs enhances their ability to thermoregulate and restore colonic temperature without altering the thermogenic activity of BAT. This response may be mediated by increasing blood flow to BAT and/or an improvement in the animal's thermal efficiency (i.e. decreased heat loss) due to a reduced reliance on shivering thermogenesis.

Adaptation, Physiological↗

PubMed2001

Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxic-ischemic insult is not neuroprotective.

Three to 12 h of mild hypothermia (HT) starting after hypoxia-ischemia is neuroprotective in piglets that are anesthetized during HT. Newborn infants suffering from neonatal encephalopathy often ventilate spontaneously and are not necessarily sedated. We aimed to test whether mild posthypoxic HT lasting 24 h was neuroprotective if the animals were not sedated. Thirty-nine piglets (median weight 1.6 kg, range 0.8-2.2 kg; median age 24 h, range 7-48 h) were anesthetized and ventilated and subjected to a 45-min hypoxic (FiO(2) approximately 6%) global insult (n = 36) or sham hypoxia (n = 3). On reoxygenation, 18 were maintained normothermic (NT, 39.0 degrees C) for 72 h, and 21 were cooled from 39 (NT) to 35 degrees C (HT) for the first 24 h before NT was resumed (18 experimental, three sham hypoxia). Cardiovascular parameters and intermittent EEG were documented throughout. The brain was perfusion fixed for neuropathology and five main areas examined using light microscopy. The insult severity (duration in minutes of EEG amplitude < 7 microV) was similar in the NT and HT groups, mean +/- SD (28 +/- 7.2 versus 27 +/- 8.6 min), as was the mean FiO(2) (5.9 +/- 0.7 versus 5.8 +/- 0.8%) during the insult. Six NT and seven HT piglets developed posthypoxic seizures that lasted 29 and 30% of the time, respectively. The distribution and degree of injury (0.0-4.0, normal-maximal damage) within the brain (hippocampus, cortex/white matter, cerebellum, basal ganglia, thalamus) were similar in the NT and HT groups (overall score, mean +/- SD, 2.3 +/- 1.5 versus 2.4 +/- 1.3) as was the EEG background amplitude at 3 h (13 +/- 3.5 versus 10 +/- 3.3 microV). The HT animals shivered and were more active. The sham control group (n = 3) shivered but had normal physiology and neuropathology. Plasma cortisol was significantly higher in the HT group during the HT period, 766 +/- 277 versus 244 +/- 144 microM at 24 h. Mild postinsult HT for 24 h was not neuroprotective in unsedated piglets and did not reduce the number of animals that developed posthypoxic seizures. Cortisol reached 3 times the NT value at the end of HT. We speculate that the stress of shivering and feeling cold interfered with the previously shown neuroprotective effect of HT. Research on the appropriateness of sedation during clinical HT is urgent.

Adult↗