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PubMed1982

Benefits of normothermic induction of blood cardioplegia in energy-depleted hearts, with maintenance of arrest by multidose cold blood cardioplegic infusions.

This study tests the hypothesis that warm induction of cardioplegia prior to prolonged maintenance by multidose infusions of cold blood cardioplegic solution would increase the tolerance of energy-depleted hearts to subsequent aortic clamping. Eighty percent depletion of subendocardial adenosine triphosphate (ATP) was produced in 30 dogs by 45 minutes of normothermic ischemia. This was followed either by unmodified blood reperfusion or 2 additional hours of aortic clamping with multidose cold blood cardioplegia. We compared a brief (5 minute) period of 37 degrees C cardioplegic induction to standard 4 degrees C blood cardioplegic induction to determine if warm induction would enhance metabolic and functional recovery. Warm cardioplegic induction resulted in more oxygen consumption than cold induction (16.9 versus 8.1 cc/100 gm), and lower levels of glucose-6-phosphate (G6P), suggesting better aerobic metabolism (0.97 versus 1.87 microM/gm wet weight). Prompt repletion of creatine phosphate (CP) occurred with warm and cold cardioplegic induction, although ATP levels levels remained low. Hearts undergoing ischemia and unmodified reperfusion consumed insufficient oxygen to meet basal metabolic needs during reperfusion (7 cc/100 gm below requirement) and recovered only 33% +/- 5% of control left ventricular performance. Better function occurred with cold cardioplegic induction (63% +/- 5%), and almost complete recovery (85% +/- 5%) occurred when warm induction of cardioplegia was used. We conclude that warm induction followed by prolonged cold multidose blood cardioplegic arrest enhances aerobic metabolism, results in normal left ventricular performance, and improves tolerance of aortic clamping in energy-depleted hearts.

Adenosine Triphosphate↗
PubMed2006

Additional freeze hardiness in wheat acquired by exposure to -3 degreesC is associated with extensive physiological, morphological, and molecular changes.

Cold-acclimated plants acquire an additional 3-5 degrees C increase in freezing tolerance when exposed to -3 degrees C for 12-18 h before a freezing test (LT50) is applied. The -3 degrees C treatment replicates soil freezing that can occur in the days or weeks leading to overwintering by freezing-tolerant plants. This additional freezing tolerance is called subzero acclimation (SZA) to differentiate it from cold acclimation (CA) that is acquired at above-freezing temperatures. Using wheat as a model, results have been obtained indicating that SZA is accompanied by changes in physiology, cellular structure, the transcriptome, and the proteome. Using a variety of assays, including DNA arrays, reverse transcription-polymerase chain reaction (RT-PCR), 2D gels with mass spectroscopic identification of proteins, and electron microscopy, changes were observed to occur as a consequence of SZA and the acquisition of added freezing tolerance. In contrast to CA, SZA induced the movement of intracellular water to the extracellular space. Many unknown and stress-related genes were upregulated by SZA including some with obvious roles in SZA. Many genes related to photosynthesis and plastids were downregulated. Changes resulting from SZA often appeared to be a loss of rather than an appearance of new proteins. From a cytological perspective, SZA resulted in alterations of organelle structure including the Golgi. The results indicate that the enhanced freezing tolerance of SZA is correlated with a wide diversity of changes, indicating that the additional freezing tolerance is the result of complex biological processes.

Acclimatization↗
PubMed1989

Topographic brain measures of human pain and pain responsivity.

Individual differences in human pain responsivity were characterized by the 1 degree C cold-pressor test. Behaviorally, a pain-tolerant group (PT = 29 Ss) tolerated the entire 3-min test (means = 180 +/- 0 sec), while a pain-sensitive group (PS = 13 Ss) averaged only 50.31 +/- 20.81 sec of the cold-pressor test (t = 16.75, P less than 0.0001), replicating our earlier studies. Physiologically, the PT group exhibited no mean differences from the PS group in cortical power densities at the baseline stage. Under the noxious stress of the cold-pressor test, both groups exhibited markedly heightened delta and beta cortical power densities. However, the PS subjects showed significantly higher delta power, but not beta power, than the PT subjects. We conclude that heightened delta activity may reflect the stress component of human pain responsivity, and that beta activity reflects the vigilance scanning of pain processes.

Adult↗
PubMed2005

Cold-inducible zinc finger-containing glycine-rich RNA-binding protein contributes to the enhancement of freezing tolerance in Arabidopsis thaliana.

Glycine-rich RNA-binding proteins (GR-RBPs) have been implicated to play roles in post-transcriptional regulation of gene expression in plants under various stress conditions, but the functional roles of GR-RBPs under stress conditions remain to be verified. Here, we examine the biological roles of a GR-RBP, designated atRZ-1a, in Arabidopsis thaliana under stress conditions. atRZ-1a was expressed ubiquitously in various Arabidopsis organs including stems, roots, leaves, flowers, and siliques. The transcript level of atRZ-1a increased markedly by cold stress, whereas its expression was marginally downregulated by drought stress or abscisic acid treatment. Germination and seedling growth of the loss-of-function mutants were retarded remarkably compared with those of the wild type under cold stress. In contrast, the transgenic Arabidopsis plants that overexpress atRZ-1a displayed earlier germination and better seedling growth than the wild type under cold stress. Moreover, the atRZ-1a-overexpressing transgenic Arabidopsis plants were more freezing tolerant than the wild-type plants. Heterologous expression of atRZ-1a in Escherichia coli demonstrated that the E. coli cells expressing atRZ-1a displayed much higher growth rate than the non-transformed cells after cold shock. These results provide evidence that atRZ-1a affects seed germination and seedling growth under low temperature and plays a role in the enhancement of freezing tolerance in Arabidopsis plants.

Arabidopsis↗
PubMed1997

The freeze-thaw stress response of the yeast Saccharomyces cerevisiae is growth phase specific and is controlled by nutritional state via the RAS-cyclic AMP signal transduction pathway.

The ability of cells to survive freezing and thawing is expected to depend on the physiological conditions experienced prior to freezing. We examined factors affecting yeast cell survival during freeze-thaw stress, including those associated with growth phase, requirement for mitochondrial functions, and prior stress treatment(s), and the role played by relevant signal transduction pathways. The yeast Saccharomyces cerevisiae was frozen at -20 degrees C for 2 h (cooling rate, less than 4 degrees C min-1) and thawed on ice for 40 min. Supercooling occurred without reducing cell survival and was followed by freezing. Loss of viability was proportional to the freezing duration, indicating that freezing is the main determinant of freeze-thaw damage. Regardless of the carbon source used, the wild-type strain and an isogenic petite mutant ([rho 0]) showed the same pattern of freeze-thaw tolerance throughout growth, i.e., high resistance during lag phase and low resistance during log phase, indicating that the response to freeze-thaw stress is growth phase specific and not controlled by glucose repression. In addition, respiratory ability and functional mitochondria are necessary to confer full resistance to freeze-thaw stress. Both nitrogen and carbon source starvation led to freeze-thaw tolerance. The use of strains affected in the RAS-cyclic AMP (RAS-cAMP) pathway or supplementation of an rca1 mutant (defective in the cAMP phosphodiesterase gene) with cAMP showed that the freeze-thaw response of yeast is under the control of the RAS-cAMP pathway. Yeast did not adapt to freeze-thaw stress following repeated freeze-thaw treatment with or without a recovery period between freeze-thaw cycles, nor could it adapt following pretreatment by cold shock. However, freeze-thaw tolerance of yeast cells was induced during fermentative and respiratory growth by pretreatment with H2O2, cycloheximide, mild heat shock, or NaCl, indicating that cross protection between freeze-thaw stress and a limited number of other types of stress exists.

Adaptation, Physiological↗
PubMed2006

Can personality traits and gender predict the response to morphine? An experimental cold pain study.

The aim of the present study was to examine the possible role of personality traits, in accordance with Cloninger's theory, and gender, in the variability of responsiveness to opioids. Specifically, it was intended to test whether or not the three personality dimensions - harm avoidance (HA), reward dependence (RD) and novelty seeking (NS) - as suggested by Cloninger, can predict inter-personal differences in responsiveness to morphine after exposure to experimental cold pain. Thirty-four healthy volunteers (15 females, 19 males) were given the cold pressor test (CPT). Pain threshold, tolerance, and magnitude (VAS) were measured before and after (six measures, 30 min apart) the administration of either 0.5 mg/kg oral morphine sulphate (n=21) or 0.33 mg/kg oral active placebo (diphenhydramine) (n=13) in a randomized, double blind design. Assessment of the three personality traits, according to Cloninger's Tridimensional Personality Questionnaire, was performed before the CPT. A high HA score (but not RD, NS, or baseline values of the three pain parameters) predicted a significantly larger pain relief following the administration of morphine sulphate (but not of the placebo). Women exhibited a larger response in response to both treatments, as indicated by a significantly increased threshold and tolerance following morphine sulphate as well as significantly increased tolerance and decreased magnitude following placebo administration. The present study confirms the existence of individual differences in response to analgesic treatment. It suggests that high HA personality trait is associated with better responsiveness to morphine treatment, and that females respond better than men to both morphine and placebo.

Adolescent↗
PubMed2001

Specific effect of venlafaxine on single and repetitive experimental painful stimuli in humans.

BACKGROUND: Tricyclic antidepressants relieve neuropathic pain, and the analgesic properties of tricyclic antidepressants are substantiated in human experimental pain models. It has been speculated that drugs with a selective inhibition of presynaptic reuptake of both serotonin and noradrenaline could have an analgesic effect comparable to the analgesic effect of tricyclic antidepressants. OBJECTIVE: Our objective was to evaluate the analgesic effect of the serotonin-noradrenaline reuptake inhibitor venlafaxine in human experimental pain models. METHOD: The study was carried out as a randomized, placebo-controlled, double-blind, crossover experiment that included 16 healthy volunteers. A 37.5-mg dose of venlafaxine was given orally 4 times with 12-hour intervals, and pain tests were performed before and 3 hours after the second and fourth doses. Pain tests included the determination of pain detection and tolerance thresholds to pressure, pain detection and tolerance thresholds on single electrical transcutaneous stimulation of the sural nerve, pain temporal summation on repetitive electrical sural nerve stimulation, and pain experienced during the cold pressor test. RESULTS: Venlafaxine increased thresholds for pain tolerance after single electrical stimulation (P =.005) and pain summation (P =.01) on repetitive stimulation but did not alter the thresholds for pain detection after single electrical sural nerve stimulation. Venlafaxine did not alter pain experienced during the cold pressor test or increase the pressure pain thresholds. CONCLUSION: Venlafaxine increases the pain tolerance threshold to electrical sural nerve stimulation and the threshold at which pain increases (pain summation). The impact of venlafaxine on pain summation in this experimental pain model on repetitive stimulation may indicate a potential analgesic effect for clinical neuropathic pain.

Adult↗
PubMed2005

Molecular characterization and origin of novel bipartite cold-regulated ice recrystallization inhibition proteins from cereals.

To understand the molecular basis of freezing tolerance in plants, several low temperature-responsive genes have been identified from wheat. Among these are two genes named TaIRI-1 and TaIRI-2 (Triticum aestivum ice recrystallization inhibition) that are up-regulated during cold acclimation in freezing-tolerant species. Phytohormones involved in pathogen defense pathways (jasmonic acid and ethylene) induce the expression of one of the two genes. The encoded proteins are novel in that they have a bipartite structure that has never been reported for antifreeze proteins. Their N-terminal part shows similarity with the leucine-rich repeat-containing regions present in the receptor domain of receptor-like protein kinases, and their C-terminus is homologous to the ice-binding domain of some antifreeze proteins. The recombinant TaIRI-1 protein inhibits the growth of ice crystals, confirming its function as an ice recrystallization inhibition protein. The TaIRI genes were found only in the species belonging to the Pooideae subfamily of cereals. Comparative genomic analysis suggested that molecular evolutionary events took place in the genome of freezing-tolerant cereals to give rise to these genes with putative novel functions. These apparent adaptive DNA rearrangement events could be part of the molecular mechanisms that ensure the survival of hardy cereals in the harsh freezing environments.

Acclimatization↗
PubMed1997

Cold stress provokes sympathoinhibitory presyncope in healthy subjects and hemodialysis patients with low cardiac output.

BACKGROUND: Sudden hypotension in progressive hypovolemia or during hemodialysis is attributed to sudden inhibition of sympathetic activity. Critical ventricular underfilling seems responsible for this paradox, but it is unknown why the transition from sympathoactivation accompanying hypovolemia to sympathoinhibition is so abrupt. We studied whether brief fluctuation of sympathetic activity induced by cold pressor test (CPT) evokes sympathoinhibition if applied during low cardiac output. METHODS AND RESULTS: Fourteen healthy subjects underwent CPT, lower-body negative pressure (LBNP; -45 mm Hg for 60 minutes), or the combination thereof. CPT alone caused vasoconstriction and increased muscle sympathetic nerve activity, followed by uneventful relaxation. When applied during reduced cardiac output, tachycardia, and vasoconstriction induced by prior LBNP for 6 minutes, CPT again caused vasoconstriction, now followed by acute hypotension in 10 subjects, and was associated with vasorelaxation, relative bradycardia, and fall in muscle sympathetic nerve activity. Eight subjects also experienced acute LBNP-induced hypotension in the absence of CPT, but not until 17 +/- 6 minutes of LBNP. We also performed CPT before and in the final phase of hemodialysis in 8 patients. Before dialysis, the patients tolerated CPT uneventfully, but during hemodialysis, CPT provoked acute hypotension in 5 cases, showing similar withdrawal of vasoconstriction. CONCLUSIONS: This is the first study showing that brief cold stress, tolerated well in normal circulatory conditions, can provoke sudden sympathoinhibition and hypotension when applied during decreased cardiac output induced by LBNP or hemodialysis. We suggest that during conditions of a decreased cardiac output, subtle sympathetic relaxation such as follows cold stress triggers self-enhancing relaxation that cannot be controlled.

Adult↗
PubMed2002

LOS2, a genetic locus required for cold-responsive gene transcription encodes a bi-functional enolase.

The Arabidopsis mutation, los2, impairs cold-responsive gene transcription, acquired freezing tolerance and plant resistance to chilling under certain conditions. LOS2 was isolated through positional cloning and shown to encode an enolase in the glycolytic pathway. In animal cells, enolase has also been known to function as a transcription factor that represses the expression of c-myc by binding to the c-myc gene promoter. LOS2 fused to green fluorescent protein is targeted to the nucleus as well as to the cytoplasm. LOS2/enolase protein can bind to the cis-element of the human c-myc gene promoter and to the gene promoter of STZ/ZAT10, a zinc finger transcriptional repressor from Arabidopsis. STZ/ZAT10 expression is induced rapidly and transiently by cold in the wild type, and this induction is stronger and more sustained in the los2 mutant. Furthermore, the expression of a RD29A-LUC reporter gene is repressed significantly by STZ/ZAT10 in transient expression assays in Arabidopsis leaves. Our results demonstrate that cold-responsive gene transcription in plants is controlled by a bi-functional enolase.

Amino Acid Sequence↗
PubMed2006

Brain-derived neurotrophic factor is critically involved in thermal-experience-dependent developmental plasticity.

All species exhibit critical period for sensory development, yet very little is known about the molecules involved in the changes in the network wiring that underlies this process. Here the role of brain-derived neurotrophic factor (BDNF) in the critical period of thermal control establishment in chicks was investigated. Neuroanatomically, the body temperature is balanced by the preoptic anterior hypothalamus (PO/AH) and controlled by thermosensitive neurons. Exposure to hot or cold conditions during the critical period of temperature control development causes a plastic change in the ratio between heat- and cold-sensitive cells and can modulate temperature tolerance. It was found that expression of BDNF mRNA but not of NGF or neurotrophin-3 was induced in the PO/AH of 3-d-old chicks during both heat and cold exposure. The peak of BDNF induction in both heat and cold exposure occurred after 6 h, with, respectively, threefold and sevenfold increases in its mRNA expression. To prove the concept that BDNF activation is a critical step in thermal-experience-dependent plasticity, BDNF was "knocked down" using antisense. It was found that, when BDNF in the PO/AH was inhibited by 80% during the third postnatal day, thermal establishment was impaired, and, after 1 week, the chicks' body temperature was reduced by 0.5 degrees C. Furthermore, later in life, their reaction to thermal challenge was altered, and they exhibited a pronounced reduction in their ability to maintain their body temperature and body weight under harsh conditions. Together, these results prove that BDNF is critically involved in thermal-experience-dependent development.

Animals↗
PubMed1999

Undermodeling affects minimal model indexes: insights from a two-compartment model.

The classic (hereafter cold) and the labeled (hereafter hot) minimal models are powerful tools to investigate glucose metabolism. The cold model provides, from intravenous glucose tolerance test (IVGTT) data, indexes of glucose effectiveness (SG) and insulin sensitivity (SI) that measure the effect of glucose and insulin, respectively, to enhance glucose disappearance and inhibit endogenous glucose production. The hot model provides, from hot IVGTT data, indexes of glucose effectiveness (SG*) and insulin sensitivity (SI*) that, respectively, measure the effects of glucose and insulin on glucose disappearance only. Recent reports call for a reexamination of some of the assumptions of the minimal models. We have previously pointed out the criticality of the single-compartment description of glucose kinetics on which both the minimal models are founded. In this paper we evaluate the impact of single-compartment undermodeling on SG, SI*, and by using a two-compartment model to describe the glucose system. The relationships of the minimal model indexes to the analogous indexes measured with the glucose clamp technique are also examined. Theoretical analysis and simulation studies indicate that cold indexes are more affected than hot indexes by undermodeling. In particular, care must be exercised in the physiological interpretation of SG, because this index is a local descriptor of events taking place in the initial portion of the IVGTT. As a consequence, SG not only reflects glucose effect on glucose uptake and production but also the rapid exchange of glucose between the accessible and nonaccessible glucose pools that occurs in the early part of the test.

Glucose↗
PubMed2004

Expression analysis of a chicory fructan 1-exohydrolase gene reveals complex regulation by cold.

The gene for a recently identified cDNA, 1-FEH IIa, encoding a fructan 1-exohydrolase was isolated and cloned from Cichorium intybus and a 1149 bp promoter fragment was characterized. An analysis of the genomic 1-FEH IIa sequence indicated that the gene (FEHIIa) consists of six introns and seven exons, which is similar to plant invertase genes. Like invertase genes, FEHIIa also contains the 9 nt mini-exon encoding the tripeptide DPN. A database search for cis-acting response elements within its promoter identified multiple elements that appear to have relevance to cold-induced expression of the gene in field-grown roots. Promoter analysis by transient expression assay demonstrated that the FEHIIa gene promoter is highly expressed in etiolated Cichorium leaves and cold-stored roots, which correlated well with the high level expression detected by RNA blot analysis. Cold also enhanced FEHIIa reporter gene expression in green leaves, however, the reporter gene activity was much lower compared with similar induction experiments in etiolated leaves. Promoter deletion analysis demonstrated the presence of potential cold-responsive ABRE and/or CRT/DRE elements in the -22 to -172 region, while regions -933 to -717 and -493 to -278 contain elements that can down-regulate expression at the conditions used. Characterization of the FEHIIa promoter may provide tools to study cold-induced expression and to increase freezing tolerance in agricultural crops.

Base Sequence↗
PubMed1995

Fentanyl prolongs lidocaine spinal anesthesia without prolonging recovery.

Lidocaine spinal anesthesia is a popular anesthetic for short procedures due to its brief duration. The addition of fentanyl may improve the quality and duration of lidocaine spinal anesthesia. Eight volunteers received plain lidocaine 5% in dextrose (50 mg) both with and without 20 micrograms of fentanyl in a randomized, double-blind, cross-over fashion. Sensory analgesia was assessed with pinprick, cold, touch, transcutaneous electrical stimulation equivalent to surgical incision, and duration of tolerance of pneumatic thigh tourniquet. Motor block was assessed with isometric force dynamometry. Regression of pinprick, touch, and cold was prolonged with fentanyl. Duration of tolerance of electrical stimulation at the umbilicus, hip, knee, and ankle was increased with fentanyl (181% increase from plain lidocaine on average; P < 0.01). Duration of tolerance of tourniquet-induced pain was increased by an average of 48% with addition of fentanyl (P = 0.02). Neither motor block nor time to void was prolonged with fentanyl. Pruritus occurred in all subjects receiving fentanyl but was treated easily and were well tolerated. We recommend the addition of 20 micrograms of fentanyl to lidocaine spinal anesthesia as a means to improve duration of sensory anesthesia without prolonging recovery of motor function or time to micturition.

Adult↗
PubMed1980

Epidural narcotics in volunteers: sensitivity to pain and to carbon dioxide.

Tolerance to pain and sensitivity to rising concentrations of inhaled carbon dioxide were measured before and after administration of methadone, 5 mg, or hydromorphone, 0.5 mg, by the intravenous route and by epidural injection in the lumbar or upper thoracic region in 5 subjects. Tolerance to periosteal pressure, cutaneous electrical stimulation and the cold pressor response to ice-water immersion were measured in both upper and lower limbs. Tolerance to all three pain modalities was greater in the epidural "blocked" limbs than in the "unblocked" limbs or after intravenous administration, and this difference was sustained after a second injection of narcotic. Sensitivity to carbon dioxide was less depressed by epidural narcotic than by intravenous administration; however, after a second dose of narcotic, depression of CO2 sensitivity by epidural injection was comparable to that produced by intravenous injection. These observations support the hypothesis that epidural narcotics have a segmental action as well as a systemic effect, and that both actions are dose-dependent.

Adult↗
PubMed1989

A primate model for the study of tonic pain, pain tolerance and diffuse noxious inhibitory controls.

A primate model of cold pressor pain is described in which the animal itself initiates all trials, may terminate painful stimuli at any time, and controls the duration of the experimental session, thus avoiding the inadvertent administration of intolerable pain stimuli. Pain tolerance time varies directly with stimulus intensity and is sensitive to motivational factors. This model will facilitate the study of endogenous pain-modulatory pathways and the assessment of analgesic treatments in animals.

Adaptation, Physiological↗
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↗