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Human physiological responses to cold exposure.

Thermal energy is transferred within and between bodies via several avenues, but for most unprotected human cold exposures, particularly during immersion, convective heat loss dominates. Lower tissue temperatures stimulate thermoreceptors, and the resultant afferent flow elicits autonomic homoeostatic responses (thermogenesis and vasoconstriction) that regulate body temperature within a narrow range. The most powerful effector responses occur when both superficial and deep thermoreceptors are cooled simultaneously, but thermoeffector activation can also occur as a result of peripheral cooling alone. The responses to cold, and the hazards associated with cold exposure, are moderated by factors which influence heat production and heat loss, including the severity and duration of cold stimuli, accompanying exercise, the magnitude of the metabolic response, and individual characteristics such as body composition, age, and gender. Cold stress can quickly overwhelm human thermoregulation with consequences ranging from impaired performance to death. This review provides a comprehensive overview of the human physiological responses to acute cold exposure.

Body Temperature Regulation↗

Influence of nicardipine on the blood pressure at rest and on the pressor responses to cold, isometric exertion, and dynamic exercise in hypertensive patients.

The dose-response effects of a new slow-calcium-channel blocker, nicardipine, on the resting blood pressure and on the pressor responses induced by skin cold, isometric exertion, and dynamic exercise were examined in a single-blind placebo-controlled study in six male patients with stable uncomplicated essential hypertension. Nicardipine was administered orally in doses of 5 mg, 10 mg, 20 mg, and 20 mg each given three times daily consecutively for 1 week. At the end of each dose period the effects on blood pressure and heart rate at rest and during the three pressor stimuli were measured. There was a significant dose-related reduction in the resting diastolic blood pressure without change in pulse pressure, accompanied by an increase in heart rate. No postural effects on blood pressure were observed. There was a small reduction in the pressor response to hand cold, which was statistically significant at the higher doses. There was no attenuation of the increases in pressure and heart rate induced by handgrip contraction or submaximal treadmill walking at any dose of nicardipine. These results are compatible with direct relaxing effect of the drug on the smooth muscle of the arteriolar resistance vessels without substantial impairment of the sympathetic influences responsible for postural control of the systemic blood pressure or those involved in the pressor responses to the three stimuli tested.

Adult↗

Genomewide transcriptional analysis of the cold shock response in Bacillus subtilis.

Previous studies with two-dimensional gel electrophoresis techniques revealed that the cold shock response in Bacillus subtilis is characterized by rapid induction and accumulation of two classes of specific proteins, which have been termed cold-induced proteins (CIPs) and cold acclimatization proteins (CAPs), respectively. Only recently, the B. subtilis two-component system encoded by the desKR operon has been demonstrated to be essential for the cold-induced expression of the lipid-modifying desaturase Des, which is required for efficient cold adaptation of the membrane in the absence of isoleucine. At present, one of the most intriguing questions in this research field is whether DesKR plays a global role in cold signal perception and transduction in B. subtilis. In this report, we present the first genomewide transcriptional analysis of a cold-exposed bacterium and demonstrate that the B. subtilis two-component system DesKR exclusively controls the desaturase gene des and is not the cold-triggered regulatory system of global relevance. In addition to this, we identified a set of genes that might participate as novel players in the cold shock adaptation of B. subtilis. Two cold-induced genes, the elongation factor homolog ylaG and the sigma(L)-dependent transcriptional activator homolog yplP, have been examined by construction and analysis of deletion mutants.

Bacillus subtilis↗

Exaggerated response to cold stress in a congenic strain for the quantitative trait locus for blood pressure.

OBJECTIVE: Stroke-prone spontaneously hypertensive rats (SHRSP) are known to have sympathetic hyperactivity to various stimuli. In the search for 'intermediate phenotypes' inferring the function of hypertension genes, the present study assessed responsiveness to cold stress in a congenic strain derived from SHRSP/Izm and Wistar-Kyoto/Izm (WKY/Izm). DESIGN: A congenic strain, WKYpch1.0, was established by 10 generations of backcrossing to transfer the chromosomal fragment between D1Wox29 and D1Arb21 of SHRSP to WKY. This fragment covered the 100:1 confidence interval of the quantitative trait locus (QTL) for blood pressure identified in a previous study. Response to cold stress was studied by exposing rats to 4 degrees C for 4 h. Blood pressure was monitored with telemetry. Urine was collected during the exposure, and urinary concentrations of catecholamines were measured by high-performance liquid chromatography. RESULTS: Under the cold stress, urinary excretion of norepinephrine (NE) and vanillylmandelic acid (VMA), as well as the plasma level of NE, was significantly greater in WKYpch1.0 than in WKY. The increase in blood pressure during the cold stress was also greater in WKYpch1.0 than in WKY. Further, neonatal chemical sympathectomy using guanethidine abolished the exaggerated response in blood pressure and in urinary excretion of NE and VMA in WKYpch1.0. CONCLUSION: These results suggested that the QTL region on rat chromosome 1 harbored genes responsible for the exaggerated response of the sympathetic nervous system to the cold stress. The relationship of this with the pathogenesis of hypertension should be elucidated in future studies.

Animals↗

Solution structure of the ribosome-associated cold shock response protein Yfia of Escherichia coli.

The solution structure of the ribosome-associated cold shock response protein Yfia of Escherichia coli was determined by nuclear magnetic resonance with a RMSD of 0.6A. Yfia shows a global beta-alpha-beta-beta-beta-alpha folding topology similar to its homologue HI0257 of Haemophilus influenzae and the double-strand-binding domain of Drosophila Staufen protein. Yfia and HI0257 differ in their surface charges and in the composition of their flexible C-termini, indicating their specificity to different target molecules. Both proteins exhibit a hydrophobic and polar region, which probably functions as interaction site for protein complex formation. Despite their similarity to the dsRBD fold, Yfia does not bind to model fragments of 16S ribosomal RNA as determined by NMR titration and gel shift experiments.

Amino Acid Sequence↗

Thermal responses to cold wind of thermoneutral and cooled subjects.

The effects of initial thermal state on thermoregulatory responses to cold (-10 degrees C) in a 0.2 (still air), 1.0, and 5.0 m. S(-1) wind speed were studied. Eight young male subjects were first preconditioned in thermoneutral (+20 degrees C, TN) or cool (-5 degrees C, CO) environment for 60 min. After preconditioning the subjects were exposed to wind at -10 degrees C in a standing position, facing the wind, for 30 min. Precooling decreased mean skin temperature (Tsk) by 4.0 (SEM 0.1) degrees C (P < 0.001) and increased heat flux by 57 (SEM 2) W x m(-2) (P < 0.001) in comparison to TN. Cooling rate of Tsk was faster (P < 0.001) in TN than in CO at every wind speed. Even so, Tsk ended up at a lower level in CO (P < 0.001-0.01) than in TN at every wind speed. Local skin temperatures of hand, finger, foot and toe were significantly lower in CO than in TN at the end of all exposures to wind. Heat flux from the skin was 8% higher (NS) in TN at 5.0 m x s(-1) wind speed in comparison to CO. A 5.0 m x s(-1) wind speed increased oxygen consumption significantly (P < 0.001) in both CO and TN in comparison to still air. At 5.0 m x s(-1) wind speed the general thermal sensation was the same (cold) in both TN and CO, despite the higher Tsk in TN. In conclusion, Tsk decreased more rapidly in TN, probably due to rapid skin vasoconstriction and redistribution of circulation to the central body. Probably for the same reason, dry heat loss from the skin was at nearly the same level in both TN and CO. Although the initial thermal state did not affect the amount of heat loss, it significantly affected the peripheral temperatures and thermal sensations and should therefore be taken into consideration in the prediction of thermophysiological responses to wind.

Adult↗

Expression profile of CBF-like transcriptional factor genes from Eucalyptus in response to cold.

Two CBF (CRT/DRE-binding factor) homologues isolated from Eucalyptus gunnii were designated EguCBF1a and EguCBF1b and belong to a gene family which includes at least five members. Both promoter and coding sequences were found to exhibit the main characteristics of a CBF transcription activator gene and, as expected, the corresponding protein targeted the nucleus. Gene expression was quantitatively analysed using real-time reverse transcription-polymerase chain reaction (RT-PCR) after a short exposure to different environmental conditions or along a two-step cold acclimation programme with either short or long daylengths. A very strong and fast response to cold was observed, with dark conditions and cold intensity (down to 0 degrees C) having a positive effect on the magnitude of induction. The two genes under study exhibited several similar features such as light response. However, interestingly, their regulation by cold proved differential and complementary as EguCBF1a was more transiently induced by a direct and intense exposure while EguCBF1b responded to milder treatments and exhibited a longer (i.e. which started earlier and finished later) time course. During acclimation, the short daylength positively affected the freezing tolerance in the same way as it positively affected the CBF transcript accumulation, suggesting a potential involvement of these genes in the adaptive response. Although very quick after the first signal, the up-regulation of the two EguCBF1 genes unexpectedly lasted throughout the chilling culture, and new inductions were seen during the thermoperiod transitions. Using a quantitative and highly sensitive measurement of gene expression combined with the application of a cold treatment consistent with natural environmental conditions, this study provides new information on the regulation of CBF-like genes by cold in planta.

Acclimatization↗

Responses to cold shock in cyanobacteria.

Acclimation of cyanobacteria to low temperatures involves induction of the expression of several families of genes. Fatty acid desaturases are responsible for maintaining the appropriate fluidity of membranes under stress conditions. RNA-binding proteins, which presumably act analogously to members of the bacterial Csp family of RNA chaperones, are involved in the maintenance of the translation under cold stress. The RNA helicase, whose expression is induced specifically by cold, might be responsible for modifying inappropriate secondary structures of RNAs induced by cold. The cold-inducible family of CIp proteins appears to be involved in the proper folding and processing of proteins. Although genes for cold-inducible proteins in cyanobacteria are heterogeneous, some common features of their untranslated regulatory regions suggest the existence of a common factor(s) that might participate in regulation of the expression of these genes under cold-stress conditions. Studies of the patterns of expression of cold-inducible genes in cyanobacteria have revealed the presence of a cold-sensing mechanism that is associated with their membrane lipids. Available information about cold-shock responses in cyanobacteria and molecular mechanisms of cold acclimation are reviewed in this article.

Adaptation, Physiological↗

Cold stress response in Archaea.

We live on a cold planet where more than 80% of the biosphere is permanently below 5 degrees C, and yet comparatively little is known about the genetics and physiology of the microorganisms inhabiting these environments. Based on molecular probe and sequencing studies, it is clear that Archaea are numerically abundant in diverse low-temperature environments throughout the globe. In addition, non-low-temperature-adapted Archaea are commonly exposed to sudden decreases in temperature, as are other microorganisms, animals, and plants. Considering their ubiquity in nature, it is perhaps surprising to find that there is such a lack of knowledge regarding low-temperature adaptation mechanisms in Archaea, particularly in comparison to what is known about archaeal thermophiles and hyperthermophiles and responses to heat shock. This review covers what is presently known about adaptation to cold shock and growth at low temperature, with a particular focus on Antarctic Archaea. The review highlights the similarities and differences that exist between Archaea and Bacteria and eukaryotes, and addresses the potentially important role that protein synthesis plays in adaptation to the cold. By reviewing the present state of the field, a number of important areas for future research are identified.

Adaptation, Physiological↗

Decrease in xenon clearance during response to cold, dry air: problems of interpretation.

In order to increase our understanding of the nasal response to cold, dry air (CDA), we studied changes in xenon clearance as an indicator of nasal blood flow. Eight individuals previously shown to respond to CDA had measurements of xenon clearance made in the left inferior turbinate before, during, and after a 15-minute exposure to either CDA (-7 degrees C to 0 degrees C, less than 10% relative humidity) or room air. The half-life in seconds for xenon clearance on the day when CDA was inhaled was 56 +/- 6, 41 +/- 5, and 110 +/- 31, before, during, and 10 minutes after challenge, respectively. On the control day, with subjects breathing room air, the equivalent measurements of half-life in seconds were 54 +/- 8, 41 +/- 6, and 42 +/- 4, respectively. Xenon clearance was prolonged significantly (p less than .01) after exposure to CDA during the clinical response. The interpretation of the change in xenon clearance as an indicator of nasal blood flow is discussed.

Air↗

Complexity of the cold acclimation response in Drosophila melanogaster.

Insects can increase their resistance to cold stress when they are exposed to non-lethal conditions prior to the stress; these plastic responses are normally described only in terms of immediate effects on mortality. Here we examine in Drosophila melanogaster the short- and longer-term effects of different conditions on several measures of cold resistance, but particularly chill coma recovery. Short-term exposure to sublethal temperature (cold hardening) did not decrease chill coma recovery times even though it decreased mortality. Exposure to 12 degrees C for 2 days (acclimation) decreased chill coma recovery times for a range of stressful temperatures when flies were cultured at 25 degrees C, but did not usually affect recovery times when flies were cultured at 19 degrees C. In contrast, 2-day exposure to 12 degrees C decreased mortality regardless of rearing temperature. Rearing at 19 degrees C decreased mortality and chill coma recovery time relative to rearing at 25 degrees C. Acclimation increased the eclosion rate of eggs from stressed females, but did not affect development time or size of the offspring. These results indicate that plastic responses to cold in D. melanogaster are complex when resistance is scored in different ways, and that effects can extend across generations.

Acclimatization↗

Thermoregulatory responses to cold transients: effects of menstrual cycle in resting women.

Effects of the menstrual cycle on heat loss and heat production (M) and core and skin temperature responses to cold were studied in six unacclimatized female nonsmokers (18-29 yr of age). Each woman, resting supine, was exposed to a cold transient (ambient temperature = mean radiant temperature = 20 to -5 degrees C at -0.32 degrees C/min, relative humidity = 50 +/- 2%, wind speed = 1 m/s) in the follicular (F) phase (days 2-6) and midluteal (L) phase (days 19-23) of her menstrual cycle. Clothed in each of two ensembles with different thermal resistances, women performed multiple experiments in the F and L phases. Thermal resistance was 0.2 and 0.4 m2 . K . W-1 for ensembles A and B, respectively. Esophageal temperature (Tes), mean weighted skin temperature (Tsk), finger temperature (Tfing), and area-weighted heat flux were recorded continuously. Rate of heat debt (-S) and integrated mean body temperature (Tb,i) were calculated by partitional calorimetry throughout the cold ramp. Extensive peripheral vasoconstriction in the F phase during early periods of the ramp elevated Tes above thermoneutral levels. Shivering thermogenesis (DeltaM = M - Mbasal, W /m2) was highly correlated with declines in Tsk and Tfing (P <0.0001). There was a reduced slope in M as a function of Tb,i in the L phase with ensembles A (P < 0.02) and B (P < 0.01). Heat flux was higher and -S was less in the L phases with ensemble A (P < 0.05). An analytic model revealed that Tsk and Tes contribute as additive inputs and Tfing has a multiplicative effect on the total control of DeltaM during cold transients (R2 = 0.9). Endogenous hormonal levels at each menstrual cycle phase, core temperature and Tsk inputs, vascular responses, and variations in body heat balance must be considered in quantifying thermoregulatory responses in women during cold stress.

Adult↗

[A study on the peripheral circulatory function and on the cold pressor response in chain saw operators (author's transl)].

Among the vibration hazards resulting from the use of vibrating tools, Raynaud's phenomenon, the peripheral nervous disturbances and the bone-joint abnormalities have been well known. Especially, Raynaud's phenomenon, which is explained as a spasm of the peripheral vascular vessels caused by disorders of the peripheral nerves or abnormalities of the arteriolae, represents the peripheral circulatory disturbance. In the worker with such a disorder of the peripheral circulatory function, it is likely that the mechanism of the cold pressor response would have been changed. The authors examined the relationship between the peripheral circulatory function and the cold pressor response in 51 chain saw operators. The following examinations were carried out: skin temperature, nail-press test and cold pressor test by 10-minute-immersion in 10 degrees C water. There was statistically an inverse correlation (r=-0.316, P < 0.025) between the increase in systolic blood pressure at the second minute during immersion and the mean skin temperature of the finger-tip during the latter half of 10-minute-immersion. It would be surmised from this result that the worker with lower peripheral circulatory function tends to increase the excitability in the sympathetic nervous system.

Adult↗

Cardiovascular responses to cold pressor and LBNP tests before and after 20-day-bedrest.

The orthostatic hypotension after weightlessness has been suggested mainly because of the blood volume reduction, and decrease in stroke volume and cardiac output as its consequence. However, since bedrest is characterized as removal of orthostasis and exercise, which are major physiological stressors to the autonomic nervous system in normal daily life of humans, thus it may be possible that general autonomic activity itself would be deconditioned in the central nervous system after bedrest. Thus, we hypothesized that 20-day bedrest may modify the cardiovascular responses to cold pressor test, which has been used to evaluate the autonomic response and which might be independent of blood volume changes. And also it was hypothesized that if there were any changes in the response to the cold pressor test, they may be related to the changes of responses to lower body negative pressure (LBNP) test.

Adult↗

Response of thermoresponsive neurons of rat's hypothalamus during intracarotid infusion of prostaglandin E2.

We investigated the effect of intracarotid infusion of prostaglandin E2 (PGE2) on the single-unit activity of neurons in the preoptic and anterior hypothalamic (PO/AH) region. A total of 35 neurons in the PO/AH region were examined: 10 were warm-responsive neurons, 6 were cold-responsive neurons, and 19 were thermally insensitive neurons. In the warm-responsive neurons, the activities of 4 neurons were facilitated, while 3 neurons were inhibited and 3 neurons were not affected after intracarotid infusion of PGE2. In the cold-responsive neurons, the activities of 2 neurons were facilitated and 4 neurons were not affected by PGE2 infusion. Furthermore, 15 out of 19 thermally insensitive neurons were not affected by PGE2 infusion. These results suggest that thermoresponsive neurons of the PO/AH region respond well to intracarotid infusion of PGE2, compared with thermally insensitive neurons. However, the direction of neuronal response induced by intracarotid infusion of PGE2 could not be generally categorized based on the thermoresponsiveness of individual neurons.

Action Potentials↗

Thromboxane A2 and prostacyclin do not modulate the systemic hemodynamic response to cold in humans.

The immersion of a limb in a mixture of water and ice induces in normal humans an initial vasoconstriction mediated mainly by catecholamine release. In some studies the cold pressor test was associated with an increase in vasoconstrictor thromboxane A2 and in vasodilating prostacyclin. Dazoxiben hydrochloride, a thromboxane synthase inhibitor, has been reported to suppress cold-induced vasoconstriction. We compared in a double-blind, crossover, placebo-controlled study the effects of indomethacin (a cyclooxygenase inhibitor), dazoxiben hydrochloride, and BM13.177 (a novel thromboxane receptor antagonist) on the changes in cutaneous vascular resistance and arterial blood pressure induced by cold in 12 healthy volunteers. Cold challenge produced an increase in blood pressure and an initial decrease in finger blood flow, reflecting an increase in cutaneous vascular resistance. Neither effective suppression of thromboxane A2 generation or of the effects of thromboxane A2 on platelets by the three active treatments nor increase in prostacyclin generation after ingestion of dazoxiben hydrochloride modified the hemodynamic response to cold. In conclusion, thromboxane A2 and prostacyclin do not play a significant role in the modulation of the systemic hemodynamic response to cold. In addition, thromboxane receptor antagonism in normal humans does not influence basal blood pressure.

6-Ketoprostaglandin F1 alpha↗

Hepatic microsomal adenosine triphosphatase and mitochondrial function. Response to cold and warm ischemia.

We investigated the response of mitochondrial function and microsomal adenosine triphosphatase (ATPase) activity in rat liver tissue subjected to in vitro ischemia at either 0 degree C to 4 degrees C or 37 degrees C for 30 to 60 minutes. Mitochondrial coupling, expressed as respiratory control index, was preserved at up to 60 minutes' cold ischemia. However, respiratory control index was decreased significantly from control by 30 minutes of warm ischemia. Both microsomal magnesium-activated ATPase and sodium-potassium ATPase activity were significantly increased by 60 minutes of warm ischemia yet were unaltered by 60 minutes of ischemia at 0 degree C to 4 degrees C. Warm ischemia produces deleterious effects on energy-generating (mitochondria) and energy-utilizing (ATPase) activity. Hypothermia provides a significant prolongation of cellular viability in ischemic tissue in terms of bioenergetic status. In addition to organ procurement and transplantation, hypothermic cytoprotection may prove valuable in areas such as shock, ischemia, and other clinical conditions of compromised visceral perfusion.

Adenosine Triphosphatases↗