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Sample records for hypothermia induced

  1. Method for inducing hypothermia

    DOEpatents

    Becker, Lance B.; Hoek, Terry Vanden; Kasza, Kenneth E.

    2003-04-15

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  2. Method for inducing hypothermia

    DOEpatents

    Becker, Lance B.; Hoek, Terry Vanden; Kasza, Kenneth E.

    2005-11-08

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  3. Method for inducing hypothermia

    DOEpatents

    Becker, Lance B.; Hoek, Terry Vanden; Kasza, Kenneth E.

    2008-09-09

    Systems for phase-change particulate slurry cooling equipment and methods to induce hypothermia in a patient through internal and external cooling are provided. Subcutaneous, intravascular, intraperitoneal, gastrointestinal, and lung methods of cooling are carried out using saline ice slurries or other phase-change slurries compatible with human tissue. Perfluorocarbon slurries or other slurry types compatible with human tissue are used for pulmonary cooling. And traditional external cooling methods are improved by utilizing phase-change slurry materials in cooling caps and torso blankets.

  4. Hypothermia.

    PubMed

    Azzopardi, D; Edwards, A D

    2007-08-01

    Experimental studies show that, following hypoxic ischaemic injury, mild induced hypothermia-a reduction of body temperature by about 3 degrees C -- preserves cerebral energy metabolism, reduces cerebral tissue injury and improves neurological function. Randomized trials in full-term and near-full-term newborns suggest that treatment with mild hypothermia is safe and improves survival without disabilities up to 18 months of age. Although the optimal time of initiation, the depth and duration, and the method of cooling are uncertain, in the absence of specific treatments many clinicians will wish to consider treating asphyxiated infants with hypothermia. Guidance now needs to be provided to promote uniform practice, to avoid inappropriate treatment and to foster continuing collaboration in future studies of neuroprotection following asphyxia. If the promising results of the current trials are confirmed by the findings from other on-going studies, with longer follow-up, the impact of such a treatment on the babies, their families and health resources in the shorter and longer terms will be considerable. PMID:17392043

  5. Hypothermia

    MedlinePlus

    ... hypothermia if you are: Very old or very young Chronically ill, especially persons who have heart or blood flow problems Malnourished Overly tired Taking certain prescription medicines Under the influence of alcohol or drugs

  6. Hypothermia

    MedlinePlus

    Cold weather can affect your body in different ways. You can get frostbite, which is frozen body tissue. Your ... Anyone who spends much time outdoors in cold weather can get hypothermia. You can also get it ...

  7. Hypothermia

    MedlinePlus

    ... That can cause hypothermia, or abnormally low body temperature. It can make you sleepy, confused, and clumsy. ... help. That makes it especially dangerous. A body temperature below 95° F is a medical emergency and ...

  8. Hyperbilirubinemia exaggerates endotoxin-induced hypothermia

    PubMed Central

    Pakai, Eszter; Garami, Andras; Nucci, Tatiane B; Ivanov, Andrei I; Romanovsky, Andrej A

    2015-01-01

    Systemic inflammation is accompanied by an increased production of reactive oxygen species (ROS) and by either fever or hypothermia (or both). To study aseptic systemic inflammation, it is often induced in rats by the intravenous administration of bacterial lipopolysaccharide (LPS). Knowing that bilirubin is a potent ROS scavenger, we compared responses to LPS between normobilirubinemic Gunn rats (heterozygous, asymptomatic; J/+) and hyperbilirubinemic Gunn rats (homozygous, jaundiced; J/J) to establish whether ROS mediate fever and hypothermia in aseptic systemic inflammation. These two genotypes correspond to undisturbed versus drastically suppressed (by bilirubin) tissue accumulation of ROS, respectively. A low dose of LPS (10 μg/kg) caused a typical triphasic fever in both genotypes, without any intergenotype differences. A high dose of LPS (1,000 μg/kg) caused a complex response consisting of early hypothermia followed by late fever. The hypothermic response was markedly exaggerated, whereas the subsequent fever response was strongly attenuated in J/J rats, as compared to J/+ rats. J/J rats also tended to respond to 1,000 μg/kg with blunted surges in plasma levels of all hepatic enzymes studied (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase), thus suggesting an attenuation of hepatic damage. We propose that the reported exaggeration of LPS-induced hypothermia in J/J rats occurs via direct inhibition of nonshivering thermogenesis by bilirubin and possibly via a direct vasodilatatory action of bilirubin in the skin. This hypothermia-exaggerating effect might be responsible, at least in part, for the observed tendency of J/J rats to be protected from LPS-induced hepatic damage. The attenuation of the fever response to 1,000 μg/kg could be due to either direct actions of bilirubin on thermoeffectors or the ROS-scavenging action of bilirubin. However, the experiments with 10 μg/kg strongly suggest that ROS signaling is

  9. Hyperbilirubinemia exaggerates endotoxin-induced hypothermia.

    PubMed

    Pakai, Eszter; Garami, Andras; Nucci, Tatiane B; Ivanov, Andrei I; Romanovsky, Andrej A

    2015-01-01

    Systemic inflammation is accompanied by an increased production of reactive oxygen species (ROS) and by either fever or hypothermia (or both). To study aseptic systemic inflammation, it is often induced in rats by the intravenous administration of bacterial lipopolysaccharide (LPS). Knowing that bilirubin is a potent ROS scavenger, we compared responses to LPS between normobilirubinemic Gunn rats (heterozygous, asymptomatic; J/+) and hyperbilirubinemic Gunn rats (homozygous, jaundiced; J/J) to establish whether ROS mediate fever and hypothermia in aseptic systemic inflammation. These two genotypes correspond to undisturbed versus drastically suppressed (by bilirubin) tissue accumulation of ROS, respectively. A low dose of LPS (10 μg/kg) caused a typical triphasic fever in both genotypes, without any intergenotype differences. A high dose of LPS (1,000 μg/kg) caused a complex response consisting of early hypothermia followed by late fever. The hypothermic response was markedly exaggerated, whereas the subsequent fever response was strongly attenuated in J/J rats, as compared to J/+ rats. J/J rats also tended to respond to 1,000 μg/kg with blunted surges in plasma levels of all hepatic enzymes studied (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase), thus suggesting an attenuation of hepatic damage. We propose that the reported exaggeration of LPS-induced hypothermia in J/J rats occurs via direct inhibition of nonshivering thermogenesis by bilirubin and possibly via a direct vasodilatatory action of bilirubin in the skin. This hypothermia-exaggerating effect might be responsible, at least in part, for the observed tendency of J/J rats to be protected from LPS-induced hepatic damage. The attenuation of the fever response to 1,000 μg/kg could be due to either direct actions of bilirubin on thermoeffectors or the ROS-scavenging action of bilirubin. However, the experiments with 10 μg/kg strongly suggest that ROS signaling is not

  10. Induced hypothermia in neurocatastrophes: feeling the chill.

    PubMed

    Wijdicks, Eelco F M

    2004-01-01

    Reducing core temperature to protect the injured brain has become a new therapeutic measure. The scientific underpinnings based on animal experiments seem sound. Evidence of the therapy's effect in human trials is insufficient or even possibly absent, but the techniques to produce moderate hypothermia are available, without apparent significant complications, and are relatively easy to use for neurointensivists. This review summarizes the mechanisms of neuroprotection due to hypothermia and its application in clinical practice. PMID:16397446

  11. Alpha-lipoic acid protects mitochondrial enzymes and attenuates lipopolysaccharide-induced hypothermia in mice

    EPA Science Inventory

    Abstract: Hypothermia is a key symptom of sepsis and the mechanism(s) leading to hypothermia during sepsis is largely unknown. To investigate a potential mechanism and find an effective treatment for hypothermia in sepsis, we induced hypothermia in mice by lipopolysaccharide (LP...

  12. Induced hypothermia for trauma-related ARDS

    PubMed Central

    Dhillon, Gagandeep; Gopal, Palepu B.; Kamat, Akshata S.; Mulavisala, K.P.

    2015-01-01

    We report a case of 27-year-old male with lung contusions related acute respiratory distress syndrome (ARDS) managed by ARDSNet guidelines and additional hypothermia. On 4th day, post trauma partial pressure of oxygen dropped to 38 mm of mercury (Hg), not improving even on high positive end-expiratory pressure of 18 cm water (H2O), inverse ratio ventilation and fraction of inspired oxygen of 1. Extracorporeal membrane oxygenation was ruled out due to the risk of hemorrhage from trauma sites. Thereafter, hypothermia along with muscle paralysis was considered to reduce total body oxygen consumption. Patient's condition improved under hypothermia, and he was extubated and taken up for fracture fixation surgeries and discharged later in stable condition. PMID:26195862

  13. Ethanol versus lipopolysaccharide-induced hypothermia: involvement of urocortin.

    PubMed

    Turek, V F; Ryabinin, A E

    2005-01-01

    The urocortin1 (Ucn1) neurons of the mid-brain-localized Edinger-Westphal nucleus (EW) are robustly responsive to ethanol (EtOH) administration, and send projections to the dorsal raphe nucleus (DRN), which contains corticotropin-releasing factor type 2 receptors (CRF2) that are responsive to Ucn1. In addition, the DRN has been shown to be involved in regulation of body temperature, a function greatly affected by EtOH administration. The goal of the present study was to identify the role that the urocortinergic projections from the EW to the DRN have in mediating EtOH-induced and lipopolysaccharide (LPS)-induced hypothermia. Male C57BL6/J mice were used. Groups of mice underwent cannulation of the DRN, and then received i.p. injections of EtOH (2g/kg) or LPS (600 microg/kg or 400 microg/kg), followed by intra-DRN injections of artificial cerebrospinal fluid (aCSF) or anti-sauvagine (aSVG) (55 pmol), a CRF2 antagonist. Separate groups of mice received single intra-DRN injections of Ucn1 (20 pmol), CRF (20 pmol) or aCSF. For all experiments, core temperatures were monitored rectally every 30 min for several hours post-injection. Both EtOH and LPS induced hypothermia, and aSVG significantly attenuated this effect after EtOH; however, there was no significant attenuation of hypothermia after either dose of LPS. Ucn1 injection also caused hypothermia, while CRF injection did not. These data demonstrate that EtOH-induced hypothermia, but not LPS-induced hypothermia, may involve Ucn1 from EW acting at CRF2 receptors in the DRN. PMID:15964490

  14. Nitrous oxide-induced hypothermia in the rat

    SciTech Connect

    Quock, R.M.; Panek, R.W.; Kouchich, F.J.; Rosenthal, M.A.

    1987-08-10

    Exposure of rats to high levels of nitrous oxide (N2O) in oxygen reduced body temperature in a concentration-related manner. The hypothermia was partly reversed by pretreatment with naloxone but not naltrexone. But in rats rendered tolerant to morphine by pellet implantation, exposure to 75% N2O/25% O2 evoked a marked hypothermia similar to that observed in morphine-naive animals. In another experiment, the hypothermic effect of chloral hydrate was also sensitive to antagonism by pretreatment with naloxone but not naltrexone. These observations lead the authors to suspect that N2O-induced hypothermia in rats is possibly not mediated by opiate receptors. The thermotropic activity of N2O may result from some non-opioid action of N2O. Its selective antagonism by naloxone (but not naltrexone) may be due to a unique non-opioid analeptic action of naloxone. 32 references, 4 figures.

  15. Coagulopathy induced by acidosis, hypothermia and hypocalcaemia in severe bleeding.

    PubMed

    De Robertis, E; Kozek-Langenecker, S A; Tufano, R; Romano, G M; Piazza, O; Zito Marinosci, G

    2015-01-01

    Acidosis, hypothermia and hypocalcaemia are determinants for morbidity and mortality during massive hemorrhages. However, precise pathological mechanisms of these environmental factors and their potential additive or synergistic anticoagulant and/or antiplatelet effects are not fully elucidated and are at least in part controversial. Best available evidences from experimental trials indicate that acidosis and hypothermia progressively impair platelet aggregability and clot formation. Considering the cell-based model of coagulation physiology, hypothermia predominantly prolongs the initiation phase, while acidosis prolongs the propagation phase of thrombin generation. Acidosis increases fibrinogen breakdown while hypothermia impairs its synthesis. Acidosis and hypothermia have additive effects. The effect of hypocalcaemia on coagulopathy is less investigated but it appears that below the cut-off of 0.9 mmol/L, several enzymatic steps in the plasmatic coagulation system are blocked while above that cut-off effects remain without clinical sequalae. The impact of environmental factor on hemostasis is underestimated in clinical practice due to our current practice of using routine coagulation laboratory tests such as partial thromboplastin time or prothrombin time, which are performed at standardized test temperature, after pH correction, and upon recalcification. Temperature-adjustments are feasible in viscoelastic point-of-care tests such as thrombelastography and thromboelastometry which may permit quantification of hypothermia-induced coagulopathy. Rewarming hypothermic bleeding patients is highly recommended because it improves patient outcome. Despite the absence of high-quality evidence, calcium supplementation is clinical routine in bleeding management. Buffer administration may not reverse acidosis-induced coagulopathy but may be essential for the efficacy of coagulation factor concentrates such as recombinant activated factor VII. PMID:24608516

  16. [Acetaminophen-induced hypothermia, an AIDS related side-effect? About 4 cases].

    PubMed

    Denes, Eric; Amaniou, Monique; Rogez, Jean-Philippe; Weinbreck, Pierre; Merle, Louis

    2002-10-01

    Hypothermia is an uncommon side effect of acetaminophen. We report 4 cases of HIV-infected patients who developed hypothermia after intravenous injection of propacetamol (the parenteral formulation of acetaminophen). The mechanism of this hypothermia is unknown. AIDS-induced changes in the metabolism of acetaminophen, could be an explanation. AIDS-associated opportunistic diseases may account for part of the mechanism. These hypothermias occur within 6 hours after the injection, are well tolerated and regress spontaneously. PMID:12486392

  17. Role of hypothermia in ethanol-induced conditioned taste aversion.

    PubMed

    Cunningham, C L; Hawks, D M; Niehus, D R

    1988-01-01

    Two experiments examined the effect of ambient temperature during ethanol exposure on development of conditioned taste aversion to saccharin. In both studies, male albino rats receiving saccharin-ethanol (1.5 g/kg, IP) pairings followed by 6-h exposure to a 32 degrees C environment developed a weaker saccharin aversion than did rats experiencing ethanol at room temperature. Exposure to the warm environment reduced ethanol-induced hypothermia, but enhanced ethanol's motor-impairing effect. The influence of ambient temperature on ethanol-induced taste aversion may be due to changes in body temperature, neural sensitivity, or elimination rate. Although alternative accounts cannot be entirely dismissed, this outcome suggests that ethanol-induced hypothermia plays a role in determining strength of conditioned taste aversion and thus may be involved in the regulation of oral ethanol intake in rats. PMID:3137617

  18. Induced Hypothermia Does Not Harm Hemodynamics after Polytrauma: A Porcine Model

    PubMed Central

    Weuster, Matthias; Mommsen, Philipp; Pfeifer, Roman; Mohr, Juliane; Ruchholtz, Steffen; Flohé, Sascha; Fröhlich, Matthias; Keibl, Claudia; Seekamp, Andreas; van Griensven, Martijn; Witte, Ingo

    2015-01-01

    Background. The deterioration of hemodynamics instantly endangers the patients' life after polytrauma. As accidental hypothermia frequently occurs in polytrauma, therapeutic hypothermia still displays an ambivalent role as the impact on the cardiopulmonary function is not yet fully understood. Methods. We have previously established a porcine polytrauma model including blunt chest trauma, penetrating abdominal trauma, and hemorrhagic shock. Therapeutic hypothermia (34°C) was induced for 3 hours. We documented cardiovascular parameters and basic respiratory parameters. Pigs were euthanized after 15.5 hours. Results. Our polytrauma porcine model displayed sufficient trauma impact. Resuscitation showed adequate restoration of hemodynamics. Induced hypothermia had neither harmful nor major positive effects on the animals' hemodynamics. Though heart rate significantly decreased and mixed venous oxygen saturation significantly increased during therapeutic hypothermia. Mean arterial blood pressure, central venous pressure, pulmonary arterial pressure, and wedge pressure showed no significant differences comparing normothermic trauma and hypothermic trauma pigs during hypothermia. Conclusions. Induced hypothermia after polytrauma is feasible. No major harmful effects on hemodynamics were observed. Therapeutic hypothermia revealed hints for tissue protective impact. But the chosen length for therapeutic hypothermia was too short. Nevertheless, therapeutic hypothermia might be a useful tool for intensive care after polytrauma. Future studies should extend therapeutic hypothermia. PMID:26170533

  19. The thermoregulatory mechanism of melatonin-induced hypothermia in chicken.

    PubMed

    Rozenboim, I; Miara, L; Wolfenson, D

    1998-01-01

    The involvement of melatonin (Mel) in body temperature (Tb) regulation was studied in White Leghorn layers. In experiment 1, 35 hens were injected intraperitoneally with seven doses of Mel (0, 5, 10, 20, 40, 80, or 160 mg Mel/kg body wt) dissolved in ethanol. Within 1 h, Mel had caused a dose-dependent reduction in Tb. To eliminate a possible vehicle effect, 0, 80, and 160 mg/kg body wt Mel dissolved in N-methyl-2-pyrrolidone (NMP) was injected. NMP had no effect on Tb, with Mel again causing a dose-dependent hypothermia. In experiment 2 (n = 30), Mel injected before exposure of layers to heat reduced Tb and prevented heat-induced hyperthermia. Injection after heat stress had begun did not prevent hyperthermia. Under cold stress, Mel induced hypothermia, which was not observed in controls. In experiment 3 (n = 12), Mel injection reduced Tb and increased metatarsal and comb temperatures (but not feathered-skin temperature), respiratory rate, and evaporative water loss. Heart rate rose and then declined, and blood pressure increased 1 h after Mel injection. Heat production rose slightly during the first hour, then decreased in parallel to the Tb decline. We conclude that pharmacological doses of Mel induce hypothermia in hens by increasing nonevaporative skin heat losses and slightly increasing respiratory evaporation. PMID:9458922

  20. Facilitation of amphetamine-induced hypothermia in mice by GABA agonists and CCK-8.

    PubMed Central

    Boschi, G.; Launay, N.; Rips, R.

    1991-01-01

    1. Amphetamine-induced hypothermia in mice is facilitated by dopaminergic stimulation and 5-hydroxytryptaminergic inhibition. The present study was designed to investigate: (a) the involvement of other neuronal systems, such as the gamma-aminobutyric acid (GABA), the opioid and the cholecystokinin (CCK-8) systems; (b) the possible contribution of hydroxylated metabolites of amphetamine to the hypothermia; (c) the capacity of dopamine itself to induce hypothermia and its mechanisms, in order to clarify the resistance of amphetamine-induced hypothermia to certain neuroleptics. 2. Pretreatment with the GABA antagonists, bicuculline and picrotoxin, did not inhibit amphetamine-induced hypothermia. The GABAB agonist, baclofen (2.5 mg kg-1, i.p.) potentiated this hypothermia, whereas the GABAA agonist, muscimol, did not. gamma-Butyrolactone (GBL) (40 mg kg-1, i.p.) and the neuropeptide CCK-8 (0.04 mg kg-1, i.p.) also induced potentiation. The opioid antagonist, naloxone, was without effect. 3. Dopamine itself (3, 9, 16 and 27 micrograms, i.c.v.) induced less hypothermia than the same doses of amphetamine. Sulpiride did not block dopamine-induced hypothermia, but pimozide (4 mg kg-1, i.p.), cis(z)flupentixol (0.25 mg kg-1, i.p.) and haloperidol (5 micrograms, i.c.v.) did. The direct dopamine receptor agonist, apomorphine, did not alter the hypothermia. Neither the 5-hydroxytryptamine (5-HT) receptor blocker, cyproheptadine, nor the inhibitor of 5-HT synthesis, p-chlorophenylalanine (PCPA), modified dopamine-induced hypothermia. Fluoxetine, an inhibitor of 5-HT reuptake, had no effect, whereas quipazine (6 mg kg-1, i.p.), a 5-HT agonist, totally prevented the hypothermia. Hypothermia was unaffected by pretreatment with CCK-8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1855128

  1. Hypothermia-induced neurite outgrowth is mediated by tumor necrosis factor-alpha.

    PubMed

    Schmitt, Katharina R L; Boato, Francesco; Diestel, Antje; Hechler, Daniel; Kruglov, Andrei; Berger, Felix; Hendrix, Sven

    2010-07-01

    Systemic or brain-selective hypothermia is a well-established method for neuroprotection after brain trauma. There is increasing evidence that hypothermia exerts beneficial effects on the brain and may also support regenerative responses after brain damage. Here, we have investigated whether hypothermia influences neurite outgrowth in vitro via modulation of the post-injury cytokine milieu. Organotypic brain slices were incubated: deep hypothermia (2 h at 17 degrees C), rewarming (2 h up to 37 degrees C), normothermia (20 h at 37 degrees C). Neurite density and cytokine release (IL 1beta, IL-6, IL-10, and TNF-alpha) were investigated after 24 h. For functional analysis mice deficient in NT-3/NT-4 and TNF-alpha as well as the TNF-alpha inhibitor etanercept were used. Hypothermia led to a significant increase of neurite outgrowth, which was independent of neurotrophin signaling. In contrast to other cytokines investigated, TNF-alpha secretion by organotypic brain slices was significantly increased after deep hypothermia. Moreover, hypothermia-induced neurite extension was abolished after administration of the TNF-alpha inhibitor and in TNF-alpha knockout mice. We demonstrate that TNF-alpha is responsible for inducing neurite outgrowth in the context of deep hypothermia and rewarming. These data suggest that hypothermia not only exerts protective effects in the CNS but may also support neurite outgrowth as a potential mechanism of regeneration. PMID:20070303

  2. Drug-induced hypothermia in stroke models: does it always protect?

    PubMed Central

    Zhang, Meijuan; Wang, Haiying; Zhao, Jinbing; Chen, Cong; Leak, Rehana K.; Xu, Yun; Vosler, Peter; Gao, Yanqin; Zhang, Feng

    2014-01-01

    Ischemic stroke is a common neurological disorder lacking a cure. Recent studies show that therapeutic hypothermia is a promising neuroprotective strategy against ischemic brain injury. Several methods to induce therapeutic hypothermia have been established; however, most of them are not clinically feasible for stroke patients. Therefore, pharmacological cooling is drawing increasing attention as a neuroprotective alternative worthy of further clinical development. We begin this review with a brief introduction to the commonly used methods for inducing hypothermia; we then focus on the hypothermic effects of eight classes of hypothermia-inducing drugs: the cannabinoids, opioid receptor activators, transient receptor potential vanilloid, neurotensins, thyroxine derivatives, dopamine receptor activators, hypothermia-inducing gases, adenosine, and adenine nucleotides. Their neuroprotective effects as well as the complications associated with their use are both considered. This article provides guidance for future clinical trials and animal studies on pharmacological cooling in the setting of acute stroke. PMID:23469851

  3. Intrathecal Opioid-Induced Hypothermia Following Subarachnoid Block With Morphine Injection for Elective Cesarean Delivery: A Case Report.

    PubMed

    Mach, John; Van Havel, Teresa; Gadwood, John; Biegner, M Andrew

    2016-02-01

    Opioids have been administered intrathecally with subarachnoid block for postoperative pain relief in parturients undergoing elective cesarean deliveries. This case report presents the uncommon occurrence of intrathecal opioid-induced hypothermia in the latent phase of recovery following elective cesarean delivery. There are few case reports on the occurrence of latent-phase postanesthesia care hypothermia in patients receiving subarachnoid block with morphine sulfate injection (Duramorph). Hypothermia can occur postoperatively for many reasons and can be life-threatening. In this case, hypothermia developed and progressed throughout the postoperative period. The causes of hypothermia were evaluated and treated without success initially. Thyroid dysfunction and alternative differential diagnoses were ruled out. Further assessment determined that the morphine injection might have been a contributing factor. Naloxone at 40-μg increments was administered intravenously and corrected the hypothermia. Awareness of hypothermia postoperatively with associated morphine administration through subarachnoid block must be ruled out in cases of progressing hypothermia. PMID:26939385

  4. THE MUSCARINIC ANTAGONIST SCOPOLAMINE ATTENUATES CHLORPYRIFOS INDUCED HYPOTHERMIA IN THE DEVELOPING RAT.

    EPA Science Inventory

    Chlorpyrifos (CHP), an anticholinesterase organophosphate (OP) pesticide, induces acute hypothermia in adult and developing rats. Previously we demonstrated that thermoregulation in preweanling pups is markedly more sensitive to the neurotoxic effects of CHP than in adults. The c...

  5. Neurotensin analog NT77 induces regulated hypothermia in the rat.

    PubMed

    Gordon, Christopher J; McMahon, Beth; Richelson, Elliott; Padnos, Beth; Katz, Laurence

    2003-10-01

    The potential use of hypothermia as a therapeutic treatment for stroke and other pathological insults has prompted the search for drugs that can lower core temperature. Ideally, a drug is needed that reduces the set-point for control of core temperature (T(c)) and thereby induces a regulated reduction in T(c). To this end, a neurotensin analog (NT77) that crosses the blood brain barrier and induces hypothermia was assessed for its effects on the set-point for temperature regulation in the Sprague-Dawley rat by measuring behavioral and autonomic thermoregulatory responses. Following surgical implanation of radiotransmitters to monitor T(c), rats were placed in a temperature gradient and allowed to select from a range of ambient temperatures (T(a)) while T(c) was monitored by radiotelemetry. There was an abrupt decrease in selected T(a) from 29 to 16 degrees C and a concomitant reduction in T(c) from 37.4 to 34.0 degrees C 1 hr after IP injection of 5.0 mg/kg NT77. Selected T(a) and T(c) then recovered to control levels by 1.5 hr and 4 hr, respectively. Oxygen consumption (M) and heat loss (H) were measured in telemetered rats housed in a direct calorimeter maintained at a T(a) of 23.5 degrees C. Injection of NT77 initially led to a reduction in M, little change in H, and marked decrease in T(c). H initially rose but decreased around the time of the maximal decrease in T(c). Overall, NT77 appears to induce a regulated hypothermic response because the decrease in T(c) was preceded by a reduction in heat production, no change in heat loss, and preference for cold T(a)'s. Inducing a regulated hypothermic response with drugs such as NT77 may be an important therapy for ischemic disease and other insults. PMID:12967685

  6. Hypothermia induced by WR-2721 in the rat.

    PubMed

    Benova, D; Kiradzhiev, G; Nikolova, M A

    1987-01-01

    Hypothermic response to a range of doses of WR-2721 (S-2-/3 aminopropylamino/-ethylthiophosphate) was studied in the rat. Time of hypothermia appearance, time and extent of maximum hypothermia, and pattern of body temperature recovery were all observed to depend upon the level of drug dose administered. The role of such hypothermia in systemic toxicity of the drug is discussed. The authors believe it to result from insufficiency of thermoregulation in small mammals, and to be of no practical importance for clinical application of the drug. PMID:2834914

  7. [Hypothermia induced alteration of refractoriness in the ventricular myocardium of ground souirrel Citellus undulatus].

    PubMed

    Kuz'min, V S; Abramov, A A; Egorov, Iu V; Rozenshtraukh, L V

    2014-12-01

    Bioelectrical activity and refractoriness in ventricular myocardium of the hibernator--ground squirrel Citellus undulatus were investigated during hypothermia. Experiments were performed with use of isolated, perfused preparations of papillary muscle from right ventricular. Preparations were obtained from hibernating (HS), summer active (SAS) squirrels and from rats. Bioelectrical activity was registered using the standard microelectrode technique at 37-17 degrees C. Action potentials duration (APD), refractoriness duration (RD) and the velocity of the action potential wave front (dV/dt) were estimated. Hypothermia induced APD and RD prolongation were demonstrated in all groups of experimental animals. However, normalized RD was significantly longer in the HS group during hypothermia than in SAS and rats. Ratio of RD to APD in HS group exceeds unity at 17 degrees C, which allows to suggest so called "postrepolarization refractoriness" during hypothermia. Also, HS reveal more prominent preservation of dV/dt during hypothermia than SAS and rat. Significant prolongation of RD and maintenance of normal excitation conduction during hypothermia probably plays essential role in hibernators resistivity to cold induced arrhythmias. PMID:25936179

  8. Thermoregulatory role of inducible nitric oxide synthase in lipopolysaccharide-induced hypothermia.

    PubMed

    Saia, Rafael S; Carnio, Evelin C

    2006-09-01

    We have tested the hypothesis that nitric oxide (NO) arising from inducible nitric oxide synthase (iNOS) plays a role in hypothermia during endotoxemia by regulating vasopressin (AVP) release. Wild-type (WT) and iNOS knockout mice (KO) were intraperitoneally injected with either saline or Escherichia coli lipopolysaccharide (LPS) 10.0 mg/kg in a final volume of 0.02 mL. Body temperature was measured continuously by biotelemetry during 24 h after injection. Three hours after LPS administration, we observed a significant drop in body temperature (hypothermic response) in WT mice, which remained until the seventh hour, returning then close to the basal level. In iNOS KO mice, we found a significant fall in body temperature after the fourth hour of LPS administration; however, the hypothermic response persisted until the end of the 24 h of the experiment. The pre-treatment with beta-mercapto-beta,beta-cyclopentamethylenepropionyl(1), O-Et-Tyr2, Val4, Arg8-Vasopressin, an AVP V1 receptor antagonist (10 microg/kg) administered intraperitoneally, abolished the persistent hypothermia induced by LPS in iNOS KO mice, suggesting the regulation of iNOS under the vasopressin release in this experimental model. In conclusion, our data suggest that the iNOS isoform plays a role in LPS-induced hypothermia, apparently through the regulation of AVP release. PMID:16714035

  9. Hypothermia-induced hyperphosphorylation: a new model to study tau kinase inhibitors

    PubMed Central

    Bretteville, Alexis; Marcouiller, François; Julien, Carl; El Khoury, Noura B.; Petry, Franck R.; Poitras, Isabelle; Mouginot, Didier; Lévesque, Georges; Hébert, Sébastien S.; Planel, Emmanuel

    2012-01-01

    Tau hyperphosphorylation is one hallmark of Alzheimer's disease (AD) pathology. Pharmaceutical companies have thus developed kinase inhibitors aiming to reduce tau hyperphosphorylation. One obstacle in screening for tau kinase inhibitors is the low phosphorylation levels of AD-related phospho-epitopes in normal adult mice and cultured cells. We have shown that hypothermia induces tau hyperphosphorylation in vitro and in vivo. Here, we hypothesized that hypothermia could be used to assess tau kinase inhibitors efficacy. Hypothermia applied to models of biological gradual complexity such as neuronal-like cells, ex vivo brain slices and adult non-transgenic mice leads to tau hyperphosphorylation at multiple AD-related phospho-epitopes. We show that Glycogen Synthase Kinase-3 inhibitors LiCl and AR-A014418, as well as roscovitine, a cyclin-dependent kinase 5 inhibitor, decrease hypothermia-induced tau hyperphosphorylation, leading to different tau phosphorylation profiles. Therefore, we propose hypothermia-induced hyperphosphorylation as a reliable, fast, convenient and inexpensive tool to screen for tau kinase inhibitors. PMID:22761989

  10. Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.

    1988-01-01

    Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation-induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia.

  11. Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.

    1988-01-01

    Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration of disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia. 34 references, 5 figures, 2 tables.

  12. Locally induced hypothermia for treatment of acute ischaemic stroke: a physical feasibility study.

    PubMed

    Slotboom, J; Kiefer, C; Brekenfeld, C; Ozdoba, C; Remonda, L; Nedeltchev, K; Arnold, M; Mattle, H; Schroth, G

    2004-11-01

    During the treatment of stroke by local intra-arterial thrombolysis (LIT) it is frequently possible to pass the blood clot with a micro-catheter, allowing perfusion of brain tissue distally to the occlusion. This possibility allows for new early treatments of ischaemic brain tissue, even before the blood clot has been removed. One potential new approach to preserve brain tissue at risk may be locally induced endovascular hypothermia. Physical parameters such as the required micro-catheter input pressure, output velocity and flow rates, and a heat exchange model, applicable in the case of a micro-catheter placed within a guiding catheter, are presented. Also, a simple cerebral temperature model is derived that models the temperature response of the brain to the perfusion with coolant fluids. Based on this model, an expression has been derived for the time needed to reach a certain cerebral target temperature. Experimental in vitro measurements are presented that confirm the usability of standard commercially available micro-catheters to induce local hypothermia of the brain. If applied in vivo, the model predicts a local cooling rate of ischaemic brain tissue of 300 g of approximately 1 degrees C in 1 min, which is up to a factor 30-times faster than the time-consuming systemic hypothermia via the skin. Systemic body temperature is only minimally affected by application of local hypothermia, thus avoiding many limitations and complications known in systemic hypothermia. PMID:15551092

  13. Anesthesia-induced hypothermia mediates decreased ARC gene and protein expression through ERK/MAPK inactivation

    PubMed Central

    Whittington, Robert A.; Bretteville, Alexis; Virág, László; Emala, Charles W.; Maurin, Thomas O.; Marcouiller, François; Julien, Carl; Petry, Franck R.; El-Khoury, Noura B.; Morin, Françoise; Charron, Jean; Planel, Emmanuel

    2013-01-01

    Several anesthetics have been reported to suppress the transcription of a number of genes, including Arc, also known as Arg3.1, an immediate early gene that plays a significant role in memory consolidation. The purpose of this study was to explore the mechanism of anesthesia-mediated depression in Arc gene and protein expression. Here, we demonstrate that isoflurane or propofol anesthesia decreases hippocampal Arc protein expression in rats and mice. Surprisingly, this change was secondary to anesthesia-induced hypothermia. Furthermore, we confirm in vivo and in vitro that hypothermia per se is directly responsible for decreased Arc protein levels. This effect was the result of the decline of Arc mRNA basal levels following inhibition of ERK/MAPK by hypothermia. Overall, our results suggest that anesthesia-induced hypothermia leads to ERK inhibition, which in turns decreases Arc levels. These data give new mechanistic insights on the regulation of immediate early genes by anesthesia and hypothermia. PMID:24045785

  14. A distinctive neurologic syndrome after induced profound hypothermia.

    PubMed

    Wical, B S; Tomasi, L G

    1990-01-01

    Four patients suffered a distinctive neurologic syndrome after undergoing profound hypothermia and complete circulatory arrest for congenital heart lesion repair. Symptom onset was delayed 24-120 hours postoperatively. The syndrome consists of choreoathetosis and oral-facial dyskinesias, hypotonia, affective changes, and pseudobulbar signs (CHAP). Precise anatomic localization is uncertain. Magnetic resonance imaging of 2 patients did not reveal basal ganglia lesions. Pathogenesis is obscure. PMID:2360962

  15. Therapeutic hypothermia protects against ischemia-induced impairment of synaptic plasticity following juvenile cardiac arrest in sex-dependent manner.

    PubMed

    Dietz, R M; Deng, G; Orfila, J E; Hui, X; Traystman, R J; Herson, P S

    2016-06-14

    Pediatric cardiac arrest (CA) often leads to poor neurologic outcomes, including deficits in learning and memory. The only approved treatment for CA is therapeutic hypothermia, although its utility in the pediatric population remains unclear. This study analyzed the effect of mild therapeutic hypothermia after CA in juvenile mice on hippocampal neuronal injury and the cellular model of learning and memory, termed long-term potentiation (LTP). Juvenile mice were subjected to cardiac arrest and cardiopulmonary resuscitation (CA/CPR) followed by normothermia (37°C) and hypothermia (30°C, 32°C). Histological injury of hippocampal CA1 neurons was performed 3days after resuscitation using hematoxylin and eosin (H&E) staining. Field excitatory post-synaptic potentials (fEPSPs) were recorded from acute hippocampal slices 7days after CA/CPR to determine LTP. Synaptic function was impaired 7days after CA/CPR. Mice exposed to hypothermia showed equivalent neuroprotection, but exhibited sexually dimorphic protection against ischemia-induced impairment of LTP. Hypothermia (32°C) protects synaptic plasticity more effectively in females, with males requiring a deeper level of hypothermia (30°C) for equivalent protection. In conclusion, male and female juvenile mice exhibit equivalent neuronal injury following CA/CPR and hypothermia protects both males and females. We made the surprising finding that juvenile mice have a sexually dimorphic response to mild therapeutic hypothermia protection of synaptic function, where males may need a deeper level of hypothermia for equivalent synaptic protection. PMID:27033251

  16. Moderate hypothermia induces marked increase in levels and nuclear accumulation of SUMO2/3-conjugated proteins in neurons

    PubMed Central

    Wang, Liangli; Ma, Qing; Yang, Wei; Mackensen, G. Burkhard; Paschen, Wulf

    2012-01-01

    Deep hypothermia protects the brain from ischemic damage and is therefore used during major cardiovascular surgeries requiring cardiopulmonary bypass and a period of circulatory arrest. Here, we demonstrated that small ubiquitin-like modifier (SUMO1-3) conjugation is markedly activated in the brain during deep to moderate hypothermia. Animals were subjected to normothermic (37°C) or deep to moderate (18°C, 24°C, 30°C) hypothermic cardiopulmonary bypass, and the effects of hypothermia on SUMO conjugation were evaluated by Western blot and immunohistochemistry. Exposure to moderate 30°C hypothermia was sufficient to markedly increased levels and nuclear accumulation of SUMO2/3-conjugated proteins in these cells. Deep hypothermia induced nuclear translocation of the SUMO conjugating enzyme Ubc9, suggesting that the increase in nuclear levels of SUMO2/3-conjugated proteins observed in brains of hypothermic animals is an active process. Exposure of primary neuronal cultures to deep hypothermia induced only a moderate rise in levels of SUMO2/3-conjugated proteins. This suggests that neurons in vivo have a higher capacity than neurons in vitro to activate this endogenous potentially neuroprotective pathway upon exposure to hypothermia. Identifying proteins that are SUMO2/3 conjugated during hypothermia could help to design new strategies for preventive and therapeutic interventions to make neurons more resistant to a transient interruption of blood supply. PMID:22891650

  17. Systemic Administration of the TRPV3 Ion Channel Agonist Carvacrol Induces Hypothermia in Conscious Rodents

    PubMed Central

    Feketa, Viktor V.; Marrelli, Sean P.

    2015-01-01

    Therapeutic hypothermia is a promising new strategy for neuroprotection. However, the methods for safe and effective hypothermia induction in conscious patients are lacking. The current study explored the Transient Receptor Potential Vanilloid 3 (TRPV3) channel activation by the agonist carvacrol as a potential hypothermic strategy. It was found that carvacrol lowers core temperature after intraperitoneal and intravenous administration in mice and rats. However, the hypothermic effect at safe doses was modest, while higher intravenous doses of carvacrol induced a pronounced drop in blood pressure and substantial toxicity. Experiments on the mechanism of the hypothermic effect in mice revealed that it was associated with a decrease in whole-body heat generation, but not with a change in cold-seeking behaviors. In addition, the hypothermic effect was lost at cold ambient temperature. Our findings suggest that although TRPV3 agonism induces hypothermia in rodents, it may have a limited potential as a novel pharmacological method for induction of hypothermia in conscious patients due to suboptimal effectiveness and high toxicity. PMID:26528923

  18. Neuroprotective effects of cold-inducible RNA-binding protein during mild hypothermia on traumatic brain injury

    PubMed Central

    Wang, Guan; Zhang, Jian-ning; Guo, Jia-kui; Cai, Ying; Sun, Hong-sheng; Dong, Kun; Wu, Cheng-gang

    2016-01-01

    Cold-inducible RNA-binding protein (CIRP), a key regulatory protein, could be facilitated by mild hypothermia in the brain, heart and liver. This study observed the effects of mild hypothermia at 31 ± 0.5°C on traumatic brain injury in rats. Results demonstrated that mild hypothermia suppressed apoptosis in the cortex, hippocampus and hypothalamus, facilitated CIRP mRNA and protein expression in these regions, especially in the hypothalamus. The anti-apoptotic effect of mild hypothermia disappeared after CIRP silencing. There was no correlation between mitogen-activated extracellular signal-regulated kinase activation and CIRP silencing. CIRP silencing inhibited extracellular signal-regulated kinase-1/2 activation. These indicate that CIRP inhibits apoptosis by affecting extracellular signal-regulated kinase-1/2 activation, and exerts a neuroprotective effect during mild hypothermia for traumatic brain injury. PMID:27335561

  19. Use of cold intravenous fluid to induce hypothermia in a comatose child after cardiac arrest due to a lightning strike.

    PubMed

    Kim, Young-Min; Jeong, Ju-Hwan; Kyong, Yeon-Young; Kim, Han-Joon; Kim, Ji-Hoon; Park, Jeong-Ho; Park, Kyu-Nam

    2008-11-01

    We report a case in which mild hypothermia was induced successfully using a cold intravenous fluid infusion in a 12-year-old boy who was comatose following 21 min of cardiac arrest caused by a lightning strike. PMID:18805616

  20. Assessing the role of the medial preoptic area in ethanol-induced hypothermia.

    PubMed

    Westerman, Ashley T; Roma, Peter G; Price, Rebecca C; Dominguez, Juan M

    2010-05-01

    Administration of ethanol produces hypothermia. The preoptic area/anterior hypothalamus (POA/AH) contains warm- and cold-sensitive neurons that are important for temperature regulation. The present study evaluated the effect of ethanol on Fos immunoreactivity (Fos-ir) in the medial preoptic area (MPOA) and the effect of lesions to the MPOA on ethanol-induced hypothermia. Rats receiving 1.5-g/kg ethanol showed an increase in Fos-ir in the MPOA. However, lesions to the MPOA did not affect core body temperature. These findings indicate that ethanol increases neural activity in the MPOA, but this increased activity does not influence ethanol-induced changes in core body temperature. PMID:20302915

  1. Hypothermia-induced ischemic tolerance is associated with Drp1 inhibition in cerebral ischemia-reperfusion injury of mice.

    PubMed

    Tang, Yingying; Liu, Xiaojie; Zhao, Jie; Tan, Xueying; Liu, Bing; Zhang, Gaofeng; Sun, Lixin; Han, Dengyang; Chen, Huailong; Wang, Mingshan

    2016-09-01

    Excessive mitochondrial fission activation has been implicated in cerebral ischemia-reperfusion (IR) injury. Hypothermia is effective in preventing cerebral ischemic damage. However, effects of hypothermia on ischemia-induced mitochondrial fission activation is not well known. Therefore, the aim of this study was to investigate whether hypothermia protect the brain by inhibiting mitochondrial fission-related proteins activation following cerebral IR injury. Adult male C57BL/6 mice were subjected to transient forebrain ischemia induced by 15min of bilateral common carotid artery occlusion (BCCAO). Mice were divided into three groups (n=48 each): Hypothermia (HT) group, with mild hypothermia (32-34°C) for 4h; Normothermia (NT) group, similarly as HT group except for cooling; Sham group, with vessels exposed but without occlusion or cooling. Hematoxylin and eosin (HE), Nissl staining, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining and behavioral testing (n=6 each) demonstrated that hypothermia significantly decreased ischemia-induced neuronal injury. The expressions of Dynamin related protein 1 (Drp1) and Cytochrome C (Cyto C) (n=6 each) in mice hippocampus were measured at 3, 6, 24, and 72h of reperfusion. IR injury significantly increased expressions of total Drp1, phosphorylated Drp1 (P-Drp1 S616) and Cyto C under normothermia. However, mild hypothermia inhibited Drp1 activation and Cyto C cytosolic release, preserved neural cells integrity and reduced neuronal necrosis and apoptosis. These findings indicated that mild hypothermia-induced neuroprotective effects against ischemia-reperfusion injury is associated with suppressing mitochondrial fission-related proteins activation and apoptosis execution. PMID:27235868

  2. Hypoxia-induced hypothermia mediated by GABA in the rostral parapyramidal area of the medulla oblongata.

    PubMed

    Osaka, T

    2014-05-16

    Hypoxia evokes a regulated decrease in the body core temperature (Tc) in a variety of animals. The neuronal mechanisms of this response include, at least in part, glutamatergic activation in the lateral preoptic area (LPO) of the hypothalamus. As the sympathetic premotor neurons in the medulla oblongata constitute a cardinal relay station in the descending neuronal pathway from the hypothalamus for thermoregulation, their inhibition can also be critically involved in the mechanisms of the hypoxia-induced hypothermia. Here, I examined the hypothesis that hypoxia-induced hypothermia is mediated by glutamate-responsive neurons in the LPO that activate GABAergic transmission in the rostral raphe pallidus (rRPa) and neighboring parapyramidal region (PPy) of the medulla oblongata in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. Unilateral microinjection of GABA (15nmol) into the rRPa and PPy regions elicited a prompt increase in tail skin temperature (Ts) and decreases in Tc, oxygen consumption rate (VO2), and heart rate. Next, when the GABAA receptor blocker bicuculline methiodide (bicuculline methiodide (BMI), 10pmol) alone was microinjected into the rRPa, it elicited unexpected contradictory responses: simultaneous increases in Ts, VO2 and heart rate and a decrease in Tc. Then, when BMI was microinjected bilaterally into the PPy, no direct effect on Ts was seen; and thermogenic and tachycardic responses were slight. However, pretreatment of the PPy with BMI, but not vehicle saline, greatly attenuated the hypothermic responses evoked by hypoxic (10%O2-90%N2, 5min) ventilation or bilateral microinjections of glutamate (5nmol, each side) into the LPO. The results suggest that hypoxia-induced hypothermia was mediated, at least in part, by the activation of GABAA receptors in the PPy. PMID:24607346

  3. Psychotropic drugs attenuate lipopolysaccharide-induced hypothermia by altering hypothalamic levels of inflammatory mediators in rats.

    PubMed

    Nassar, Ahmad; Sharon-Granit, Yael; Azab, Abed N

    2016-07-28

    Recent evidence suggests that inflammation may contribute to the pathophysiology of mental disorders and that psychotropic drugs exert various effects on brain inflammation. The administration of bacterial endotoxin (lipopolysaccharide, LPS) to mammals is associated with robust production of inflammatory mediators and pathological changes in body temperature. The objective of the present study was to examine the effects of four different psychotropic drugs on LPS-induced hypothermia and production of prostaglandin (PG) E2, tumor necrosis factor (TNF)-α and phosphorylated-p65 (P-p65) levels in hypothalamus of LPS-treated rats. Rats were treated once daily with lithium (100mg/kg), carbamazepine (40mg/kg), haloperidol (2mg/kg), imipramine (20mg/kg) or vehicle (NaCl 0.9%) for 29 days. On day 29, rats were injected with LPS (1mg/kg) or saline. At 1.5h post LPS injection body temperature was measured, rats were sacrificed, blood was collected and their hypothalami were excised, homogenized and centrifuged. PGE2, TNF-α and nuclear P-p65 levels were determined by specific ELISA kits. We found that lithium, carbamazepine, haloperidol and imipramine significantly attenuated LPS-induced hypothermia, resembling the effect of classic anti-inflammatory drugs. Moreover, lithium, carbamazepine, haloperidol and imipramine differently but significantly affected the levels of PGE2, TNF-α and P-p65 in plasma and hypothalamus of LPS-treated rats. The results suggest that psychotropic drugs attenuate LPS-induced hypothermia by reducing hypothalamic production of inflammatory constituents, particularly PGE2. The effects of psychotropic drugs on brain inflammation may contribute to their therapeutic mechanism but also to their toxicological profile. PMID:27181513

  4. Neuroprotective effects of bloodletting at Jing points combined with mild induced hypothermia in acute severe traumatic brain injury

    PubMed Central

    Tu, Yue; Miao, Xiao-mei; Yi, Tai-long; Chen, Xu-yi; Sun, Hong-tao; Cheng, Shi-xiang; Zhang, Sai

    2016-01-01

    Bloodletting at Jing points has been used to treat coma in traditional Chinese medicine. Mild induced hypothermia has also been shown to have neuroprotective effects. However, the therapeutic effects of bloodletting at Jing points and mild induced hypothermia alone are limited. Therefore, we investigated whether combined treatment might have clinical effectiveness for the treatment of acute severe traumatic brain injury. Using a rat model of traumatic brain injury, combined treatment substantially alleviated cerebral edema and blood-brain barrier dysfunction. Furthermore, neurological function was ameliorated, and cellular necrosis and the inflammatory response were lessened. These findings suggest that the combined effects of bloodletting at Jing points (20 μL, twice a day, for 2 days) and mild induced hypothermia (6 hours) are better than their individual effects alone. Their combined application may have marked neuroprotective effects in the clinical treatment of acute severe traumatic brain injury. PMID:27482221

  5. Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats.

    PubMed

    Ma, Junwei; Wang, Zhong; Liu, Chenglin; Shen, Haitao; Chen, Zhouqing; Yin, Jia; Zuo, Gang; Duan, Xiaochun; Li, Haiying; Chen, Gang

    2016-01-01

    Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33-36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3β pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3β signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3β signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3β signaling pathway. PMID:27026509

  6. Monitoring of pain and stress in an infant with asphyxia during induced hypothermia: a case report.

    PubMed

    Hoffman, Karin; Bromster, Therése; Hakansson, Stellan; van den Berg, Johannes

    2013-08-01

    The purpose of this article was to study an infant who suffered from asphyxia undergoing induced hypothermia with regard to (1) describe the pain and stress as measured by physiological variables skin conductance algesimeter (SCA) and pain rating scales, (2) the correlation between SCA and pain rating scales, and (3) how temperature cycles in the cooling blanket affect the response of the sympathetic nervous system as measured by the SCA and physiological variables. A single prospective case study was used for this article. Data were recorded every 15 minutes for 96 hours. Each observation was categorized according to treatment phase: cooling 0 to 72 hours, rewarming, and controlled normal temperature up to 96 hours. Structured observations were carried out and all nursing care was documented. In addition, 5 periods with no other nursing interventions were identified in which data were recorded every minute for analysis. Skin conductance algimetry showed a variable response during treatment. During cooling, 68% of the 15-minute periods, signs of stress and pain were recorded. During rewarming, the corresponding figure was 83%. During the time sequences with normal temperature, 89% of the periods were associated with stress and pain. During 80% of the nursing procedures, the SCA showed stress and pain. There was no correlation between the pain-rating scales and SCA. When the cooling blanket temperature was lower than core temperature, the infant had more stress and pain according to SCA (P < .001) and an increase in heart rate and blood pressure (P < .001). In infants during induced hypothermia, SCA seem to detect pain and stress. Future evaluation of SCA for the detection of pain and stress during hypothermia treatment is necessary. Pain-rating scales do not appear reliable in this case report. PMID:23912017

  7. Chlorpyrifos-induced hypothermia and vasodilation in the tail of the rat: blockade by scopolamine.

    PubMed

    Gordon, C J; Yang, Y L

    2000-07-01

    Organophosphate pesticides such as chlorpyrifos reduce core temperature (Tc) in laboratory rodents. The mechanism(s) responsible for the chlorpyrifos-induced hypothermia are not well known. This study assessed the role of a key effector for thermoregulation in the rat, vasomotor control of heat loss from the tail, and its possible cholinergic control during chlorpyrifos-induced hypothermia. Tc and motor activity were monitored by telemetry in female Long-Evans rats maintained at an ambient temperature (Ta) of 25 degrees. Tail skin temperature (Tsk(t)) was measured hourly. Rats were dosed with chlorpyrifos (0 or 25 mg/kg orally). Two hr later the rats were dosed with saline or scopolamine (1.0 mg/kg intraperitoneally). Two hr after chlorpyrifos treatment there was a marked elevation in Tsk(t)) concomitant with a 0.5 degrees reduction in Tc. Scopolamine administered to control rats led to a marked elevation in Tc with little change in Tsk(t). Rats treated with chlorpyrifos and administered scopolamine underwent a marked vasoconstriction and elevation in Tc. Vasodilation of the tail is an important thermoeffector to reduce Tc during the acute stages of chlorpyrifos exposure. The blockade of the response by scopolamine suggests that the hypothermic and vasodilatory response to chlorpyrifos is mediated via a cholinergic muscarinic pathway in the CNS. PMID:10987209

  8. Sodium selenite-induced hypothermia in mice: indirect evidence for a neural effect.

    PubMed

    Watanabe, C; Suzuki, T

    1986-12-01

    The effect of sodium selenite (SS) on the body temperature of adult male ICR mice was examined. SS (10-60 mumol/kg) administered subcutaneously resulted in a transient and dose-dependent hypothermia at ambient temperatures (Ta) of 20 and 30 degrees C. Reduced oxygen consumption accompanied the changes in body temperature. In addition, SS-treated mice exhibited transient cold-seeking behavior in the thermogradient. This SS-induced hypothermia was very similar to those induced by ethanol, tetrahydrocannabinol, triethyltin, sulfolane, and chlordimeform in that these all were transient, dependent on Ta, and not counteracted by behavioral thermoregulation. From these results, involvement of neural afferent or integral pathways is suggested. Further, acute mortality of SS-injected mice was enhanced with the elevation of Ta, as in the case of the chemicals mentioned above. Considering the diverse chemical and pharmacological properties of these chemicals, these results may suggest a possible interrelation between the hypothermic response and the modification of toxicity. PMID:3787631

  9. Early Combined Therapy with Pharmacologically Induced Hypothermia and Edaravone Exerts Neuroprotective Effects in a Rat Model of Intracerebral Hemorrhage.

    PubMed

    Zhu, Yonglin; Liu, Chunling; Sun, Zhikun

    2015-11-01

    In present study, we evaluated acute neuroprotective effects of combined therapy with pharmacologically induced hypothermia and edaravone in a rat model of intracerebral hemorrhage (ICH). ICH was caused by injection of 0.5 U of collagenase VII to the caudate nucleus of male Sprague-Dawley rats. Sham-treated animals receive injections of normal saline instead of collagenase VII. All animals were randomly divided into five groups: sham group, ICH group, hypothermia group, edavarone (10 mg/kg) group, and combined hypothermia + edavarone group. Hypothermia was induced by injection of the second-generation neurotensin receptor agonist HPI-201 (2 mg/kg at 1 h after ICH; 1 mg/kg at 4 and 7 h after ICH). Hypothermia was sustained for at least 6 h. The study outcomes were the extent of brain edema, permeability of the blood-brain barrier (Evan's blue dye), expression of matrix metalloproteinase-9 and inflammatory cytokines (IL-1β, IL-4, IL-6, and TNF-α), and expression of apoptosis-related proteins (caspase-3, cytochrome C, Bcl-2, and Bax). Brain edema, permeability of the blood-brain barrier, and expression of metalloproteinase-9 were increased, while expression of caspase-3 and Bcl-2 was decreased by ICH. We observed that the combined therapy was significantly more potent in reverting the above negative trends induced by ICH. In conclusion, our results indicate that a combination of pharmacologically induced hypothermia and edavarone leads to potentiation of their respective neuroprotective effects. PMID:27352357

  10. An unusual autopsy case of lethal hypothermia exacerbated by body lice-induced severe anemia.

    PubMed

    Nara, Akina; Nagai, Hisashi; Yamaguchi, Rutsuko; Makino, Yohsuke; Chiba, Fumiko; Yoshida, Ken-ichi; Yajima, Daisuke; Iwase, Hirotaro

    2016-05-01

    Pediculus humanus humanus (known as body lice) are commonly found in the folds of clothes, and can cause skin disorders when they feed on human blood, resulting in an itching sensation. Body lice are known as vectors of infectious diseases, including typhus, recurrent fever, and trench fever. An infestation with blood-sucking body lice induces severe cutaneous pruritus, and this skin disorder is known as "vagabond's disease." A body lice infestation is sometimes complicated with iron deficiency anemia. In the present case, a man in his late 70s died of lethal hypothermia in the outdoors during the winter season. The case history and autopsy findings revealed that the cause of the lethal hypothermia was iron deficiency anemia, which was associated with a prolonged infestation of blood-sucking body lice. Also, he had vagabond's disease because the skin on his body was abnormal and highly pigmented. This is an unusual autopsy case since the body lice contributed to the cause of the death. PMID:26384507

  11. Platelet Dynamics during Natural and Pharmacologically Induced Torpor and Forced Hypothermia

    PubMed Central

    de Vrij, Edwin L.; Vogelaar, Pieter C.; Goris, Maaike; Houwertjes, Martin C.; Herwig, Annika; Dugbartey, George J.; Boerema, Ate S.; Strijkstra, Arjen M.; Bouma, Hjalmar R.; Henning, Robert H.

    2014-01-01

    Hibernation is an energy-conserving behavior in winter characterized by two phases: torpor and arousal. During torpor, markedly reduced metabolic activity results in inactivity and decreased body temperature. Arousal periods intersperse the torpor bouts and feature increased metabolism and euthermic body temperature. Alterations in physiological parameters, such as suppression of hemostasis, are thought to allow hibernators to survive periods of torpor and arousal without organ injury. While the state of torpor is potentially procoagulant, due to low blood flow, increased viscosity, immobility, hypoxia, and low body temperature, organ injury due to thromboembolism is absent. To investigate platelet dynamics during hibernation, we measured platelet count and function during and after natural torpor, pharmacologically induced torpor and forced hypothermia. Splenectomies were performed to unravel potential storage sites of platelets during torpor. Here we show that decreasing body temperature drives thrombocytopenia during torpor in hamster with maintained functionality of circulating platelets. Interestingly, hamster platelets during torpor do not express P-selectin, but expression is induced by treatment with ADP. Platelet count rapidly restores during arousal and rewarming. Platelet dynamics in hibernation are not affected by splenectomy before or during torpor. Reversible thrombocytopenia was also induced by forced hypothermia in both hibernating (hamster) and non-hibernating (rat and mouse) species without changing platelet function. Pharmacological torpor induced by injection of 5′-AMP in mice did not induce thrombocytopenia, possibly because 5′-AMP inhibits platelet function. The rapidness of changes in the numbers of circulating platelets, as well as marginal changes in immature platelet fractions upon arousal, strongly suggest that storage-and-release underlies the reversible thrombocytopenia during natural torpor. Possibly, margination of platelets

  12. Therapeutic Effects of Pharmacologically Induced Hypothermia against Traumatic Brain Injury in Mice

    PubMed Central

    Lee, Jin Hwan; Wei, Ling; Gu, Xiaohuan; Wei, Zheng; Dix, Thomas A.

    2014-01-01

    Abstract Preclinical and clinical studies have shown therapeutic potential of mild-to-moderate hypothermia for treatments of stroke and traumatic brain injury (TBI). Physical cooling in humans, however, is usually slow, cumbersome, and necessitates sedation that prevents early application in clinical settings and causes several side effects. Our recent study showed that pharmacologically induced hypothermia (PIH) using a novel neurotensin receptor 1 (NTR1) agonist, HPI-201 (also known as ABS-201), is efficient and effective in inducing therapeutic hypothermia and protecting the brain from ischemic and hemorrhagic stroke in mice. The present investigation tested another second-generation NTR1 agonist, HPI-363, for its hypothermic and protective effect against TBI. Adult male mice were subjected to controlled cortical impact (CCI) (velocity=3 m/sec, depth=1.0 mm, contact time=150 msec) to the exposed cortex. Intraperitoneal administration of HPI-363 (0.3 mg/kg) reduced body temperature by 3–5°C within 30–60 min without triggering a shivering defensive reaction. An additional two injections sustained the hypothermic effect in conscious mice for up to 6 h. This PIH treatment was initiated 15, 60, or 120 min after the onset of TBI, and significantly reduced the contusion volume measured 3 days after TBI. HPI-363 attenuated caspase-3 activation, Bax expression, and TUNEL-positive cells in the pericontusion region. In blood–brain barrier assessments, HPI-363 ameliorated extravasation of Evans blue dye and immunoglobulin G, attenuated the MMP-9 expression, and decreased the number of microglia cells in the post-TBI brain. HPI-363 decreased the mRNA expression of tumor necrosis factor-α and interleukin-1β (IL-1β), but increased IL-6 and IL-10 levels. Compared with TBI control mice, HPI-363 treatments improved sensorimotor functional recovery after TBI. These findings suggest that the second generation NTR-1 agonists, such as HPI-363, are efficient

  13. Pharmacologically induced hypothermia via TRPV1 channel agonism provides neuroprotection following ischemic stroke when initiated 90 min after reperfusion

    PubMed Central

    Cao, Zhijuan; Balasubramanian, Adithya

    2013-01-01

    Traditional methods of therapeutic hypothermia show promise for neuroprotection against cerebral ischemia-reperfusion (I/R), however, with limitations. We examined effectiveness and specificity of pharmacological hypothermia (PH) by transient receptor potential vanilloid 1 (TRPV1) channel agonism in the treatment of focal cerebral I/R. Core temperature (Tcore) was measured after subcutaneous infusion of TRPV1 agonist dihydrocapsaicin (DHC) in conscious C57BL/6 WT and TRPV1 knockout (KO) mice. Acute measurements of heart rate (HR), mean arterial pressure (MAP), and cerebral perfusion were measured before and after DHC treatment. Focal cerebral I/R (1 h ischemia + 24 h reperfusion) was induced by distal middle cerebral artery occlusion. Hypothermia (>8 h) was initiated 90 min after start of reperfusion by DHC infusion (osmotic pump). Neurofunction (behavioral testing) and infarct volume (TTC staining) were measured at 24 h. DHC (1.25 mg/kg) produced a stable drop in Tcore (33°C) in naive and I/R mouse models but not in TRPV1 KO mice. DHC (1.25 mg/kg) had no measurable effect on HR and cerebral perfusion but produced a slight transient drop in MAP (<6 mmHg). In stroke mice, DHC infusion produced hypothermia, decreased infarct volume by 87%, and improved neurofunctional score. The hypothermic and neuroprotective effects of DHC were absent in TRPV1 KO mice or mice maintained normothermic with heat support. PH via TRPV1 agonist appears to be a well-tolerated and effective method for promoting mild hypothermia in the conscious mouse. Furthermore, TRPV1 agonism produces effective hypothermia in I/R mice and significantly improves outcome when initiated 90 min after start of reperfusion. PMID:24305062

  14. Induced Hypothermia During Resuscitation From Hemorrhagic Shock Attenuates Microvascular Inflammation In The Rat Mesenteric Microcirculation

    PubMed Central

    Coyan, Garrett N.; Moncure, Michael; Thomas, James H.; Wood, John G.

    2014-01-01

    Introduction Microvascular inflammation occurs during resuscitation following hemorrhagic shock, causing multiple organ dysfunction and mortality. Pre-clinical evidence suggests that hypothermia may have some benefit in selected patients by decreasing this inflammation, but this effect has not been extensively studied. Methods Intravital microscopy was used to visualize mesenteric venules of anesthetized rats in real time to evaluate leukocyte adherence and mast cell degranulation. Animals were randomly allocated to normotensive or hypotensive groups, and further subdivided into hypothermic and normothermic resuscitation (N=6 per group). Animals in the shock groups underwent mean arterial blood pressure reduction to 40-45 mmHg for 1 hour via blood withdrawal. During the first two hours following resuscitation by infusion of shed blood plus double that volume of normal saline, rectal temperature of the hypothermic groups were maintained at 32-34°C, while the normothermic groups were maintained between 36-38°C. The hypothermic group was then rewarmed for the final two hours of resuscitation. Results Leukocyte adherence was significantly lower after 2 hours of hypothermic resuscitation compared with normothermic resuscitation: (2.8±0.8 vs 8.3±1.3 adherent leukocytes, p=0.004). Following rewarming, leukocyte adherence remained significantly different between hypothermic and normothermic shock groups: (4.7±1.2 vs 9.5±1.6 adherent leukocytes, p=0.038). Mast cell degranulation index (MDI) was significantly decreased in the hypothermic (1.02±0.04 MDI) vs normothermic (1.22±0.07 MDI) shock groups (p=0.038) after the experiment. Conclusions Induced hypothermia during resuscitation following hemorrhagic shock attenuates microvascular inflammation in rat mesentery. Furthermore, this decrease in inflammation is carried over after rewarming takes place. PMID:25046540

  15. Apoptosis-inducing effects of cetuximab combined with radiotherapy and hypothermia on human nasopharyngeal carcinoma CNE cells

    PubMed Central

    Liu, Wenqi; Kang, Min; Qin, Yutao; Wei, Zhuxin; Wang, Rensheng

    2015-01-01

    To investigate the apoptosis-inducing effects of cetuximab combined with radiotherapy and hypothermia in human nasopharyngeal carcinoma CNE cells. CNE cells were treated with the radiation monotherapy, the radiation and hypothermia, the cetuximab and radiation, and the triple-combination treatment, respectively. MTT assay was performed to assess cell proliferation following treatments. Hoechst 33258 staining and flow cytometry analyses were used to detect apoptotic process. Western blot analysis was performed to determine the protein expression levels. Cetuximab monotherapy inhibited the proliferation of CNE cells. Hyperthermia alone inhibited EGFR expression, and prolonged hypothermia treatment resulted in declining EGFR expression levels in these cells. Moreover, Hoechst 33258 staining showed obvious apoptotic morphologies in the treatment groups. Flow cytometry analysis showed that the interventions dramatically increased the apoptosis rates in CNE cells, with the most potent effect for the triple-combination treatment. Western blot analysis showed that, in the treatment groups, the expression levels of Bax were increased, while the expression levels of Bcl-2 were decreased, leading to significantly elevated Bax/Bcl-2 ratios in these groups, with the highest ratio for the triple-combination treatment. Cetuximab combined with radiotherapy and hypothermia treatments could efficiently inhibit the proliferation of CNE cells, and enhance the cellular apoptotic processes via regulating the expression levels of Bax and Bcl-2. Our findings provide experimental evidence for the application of the combination therapy in clinical treatment of nasopharyngeal carcinoma. PMID:25932149

  16. Pramipexole-Induced Hypothermia Reduces Early Brain Injury via PI3K/AKT/GSK3β pathway in Subarachnoid Hemorrhage rats

    PubMed Central

    Ma, Junwei; Wang, Zhong; Liu, Chenglin; Shen, Haitao; Chen, Zhouqing; Yin, Jia; Zuo, Gang; Duan, Xiaochun; Li, Haiying; Chen, Gang

    2016-01-01

    Previous studies have shown neuroprotective effects of hypothermia. However, its effects on subarachnoid hemorrhage (SAH)-induced early brain injury (EBI) remain unclear. In this study, a SAH rat model was employed to study the effects and mechanisms of pramipexole-induced hypothermia on EBI after SAH. Dose-response experiments were performed to select the appropriate pramipexole concentration and frequency of administration for induction of mild hypothermia (33–36 °C). Western blot, neurobehavioral evaluation, Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Fluoro-Jade B (FJB) staining were used to detect the effects of pramipexole-induced hypothermia on SAH-induced EBI, as well as to study whether controlled rewarming could attenuate these effects. Inhibitors targeting the PI3K/AKT/GSK3β pathway were administered to determine whether the neuroprotective effect of pramipexole-induced hypothermia was mediated by PI3K/AKT/GSK3β signaling pathway. The results showed that intraperitoneal injection of pramipexole at 0.25 mg/kg body weight once per 8 hours was found to successfully and safely maintain rats at mild hypothermia. Pramipexole-induced hypothermia ameliorated SAH-induced brain cell death, blood-brain barrier damage and neurobehavioral deficits in a PI3K/AKT/GSK3β signaling-dependent manner. Therefore, we may conclude that pramipexole-induced hypothermia could effectively inhibit EBI after SAH in rats via PI3K/AKT/GSK3β signaling pathway. PMID:27026509

  17. Hibernation, Hypothermia and a Possible Therapeutic "Shifted Homeostasis" Induced by Central Activation of A1 Adenosine Receptor (A1AR).

    PubMed

    Tupone, Domenico; Cetas, Justin S; Morrison, Shaun F

    2016-04-01

    The positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Pharmacological manipulation of central autonomic thermoregulatory circuits could represent a potential target for the induction of a hypothermic state. Here we present a brief description of the CNS thermoregulatory centers and how the manipulation of these circuits can be useful in the treatment of pathological conditions such as stroke or brain hemorrhage. PMID:27333659

  18. FACTORS INFLUENCING DIISOPROPYL FLUOROPHOSPHATE-INDUCED HYPOTHERMIA AND HYPERTHERMIA IN THE RAT

    EPA Science Inventory

    Exposing rats to the anticholinesterase (antiChE) diisopropyl fluorophosphate (DFP) causes a transient hypothermia lasting approximately 24 hours followed by a period of hyperthermia lasting approximately 48 hours. ince a fever is a predominant thermoregulatory response in humans...

  19. Effect of Hypothermia-Induced Respiratory Arrest on Cerebral Circulation in Rats.

    PubMed

    Mel'nikova, N N; Petrova, L A

    2016-03-01

    Intravital microscopy was employed to examine cerebral circulation in rats assessed by blood flow in the venules with diameter of 10-30 μ during immersion hypothermia continued to the moment of respiratory arrest and for 10 min thereafter. Circulation in the cerebral microvessels continued during severe hypothermia, and it went on even after hypothermic respiratory arrest while the heart was beating. In pial venules, the blood continued to fl ow for 8-10 min after respiratory arrest. PMID:27021108

  20. Ambient temperature effects on taste aversion conditioned by ethanol: contribution of ethanol-induced hypothermia.

    PubMed

    Cunningham, C L; Niehus, J S; Bachtold, J F

    1992-12-01

    Six experiments examined the effects of low (5-10 degrees C), normal (21 degrees C), or high (32 degrees) ambient temperature on conditioned taste aversion and body temperature changes produced by ethanol, lithium chloride, or morphine sulfate. Fluid-deprived rats received five to seven taste conditioning trials at 48-hr intervals. On each trial, access to saccharin at normal ambient temperature was followed by injection of drug or saline and placement for 6 hr into a temperature-controlled enclosure. Exposure to low ambient temperature facilitated, whereas exposure to high ambient temperature retarded acquisition of ethanol-induced conditioned taste aversion. The ability of an alteration in ambient temperature to influence conditioned taste aversion varied as a function of ethanol dose and was related to ambient temperature's effect on ethanol-induced hypothermia. More specifically, strength of conditioned taste aversion was negatively correlated with core body temperature after ethanol injection. Alterations in ambient temperature alone did not affect ingestion of a paired flavor solution in the absence of drug. Moreover, alterations in ambient temperature did not appear to influence conditioned taste aversion by changing ethanol pharmacokinetics. Finally, high and low ambient temperature did not affect development of taste aversion conditioned by lithium chloride or morphine sulfate. The overall pattern of data presented by these experiments supports the hypothesis that ambient-temperature influences strength of ethanol-induced conditioned taste aversion by altering the hypothermic response to ethanol. More generally, these data support the suggestion that body temperature change induced by ethanol is related to ethanol's aversive motivational effects and may be involved in modulating ethanol intake. PMID:1471766

  1. Drug-induced mild therapeutic hypothermia obtained by administration of a transient receptor potential vanilloid type 1 agonist

    PubMed Central

    2010-01-01

    Background The use of mechanical/physical devices for applying mild therapeutic hypothermia is the only proven neuroprotective treatment for survivors of out of hospital cardiac arrest. However, this type of therapy is cumbersome and associated with several side-effects. We investigated the feasibility of using a transient receptor potential vanilloid type 1 (TRPV1) agonist for obtaining drug-induced sustainable mild hypothermia. Methods First, we screened a heterogeneous group of TRPV1 agonists and secondly we tested the hypothermic properties of a selected candidate by dose-response studies. Finally we tested the hypothermic properties in a large animal. The screening was in conscious rats, the dose-response experiments in conscious rats and in cynomologus monkeys, and the finally we tested the hypothermic properties in conscious young cattle (calves with a body weight as an adult human). The investigated TRPV1 agonists were administered by continuous intravenous infusion. Results Screening: Dihydrocapsaicin (DHC), a component of chili pepper, displayed a desirable hypothermic profile with regards to the duration, depth and control in conscious rats. Dose-response experiments: In both rats and cynomologus monkeys DHC caused a dose-dependent and immediate decrease in body temperature. Thus in rats, infusion of DHC at doses of 0.125, 0.25, 0.50, and 0.75 mg/kg/h caused a maximal ΔT (°C) as compared to vehicle control of -0.9, -1.5, -2.0, and -4.2 within approximately 1 hour until the 6 hour infusion was stopped. Finally, in calves the intravenous infusion of DHC was able to maintain mild hypothermia with ΔT > -3°C for more than 12 hours. Conclusions Our data support the hypothesis that infusion of dihydrocapsaicin is a candidate for testing as a primary or adjunct method of inducing and maintaining therapeutic hypothermia. PMID:20932337

  2. Fasting induces ketoacidosis and hypothermia in PDHK2/PDHK4-double-knockout mice

    PubMed Central

    Jeoung, Nam Ho; Rahimi, Yasmeen; Wu, Pengfei; Lee, W. N. Paul; Harris, Robert A.

    2015-01-01

    The importance of PDHK (pyruvate dehydrogenase kinase) 2 and 4 in regulation of the PDH complex (pyruvate dehydrogenase complex) was assessed in single- and double-knockout mice. PDHK2 deficiency caused higher PDH complex activity and lower blood glucose levels in the fed, but not the fasted, state. PDHK4 deficiency caused similar effects, but only after fasting. Double deficiency intensified these effects in both the fed and fasted states. PDHK2 deficiency had no effect on glucose tolerance, PDHK4 deficiency produced only a modest effect, but double deficiency caused a marked improvement and also induced lower insulin levels and increased insulin sensitivity. In spite of these beneficial effects, the double-knockout mice were more sensitive than wild-type and single-knockout mice to long-term fasting, succumbing to hypoglycaemia, ketoacidosis and hypothermia. Stable isotope flux analysis indicated that hypoglycaemia was due to a reduced rate of gluconeogenesis and that slightly more glucose was converted into ketone bodies in the double-knockout mice. The findings establish that PDHK2 is more important in the fed state, PDHK4 is more important in the fasted state, and survival during long-term fasting depends upon regulation of the PDH complex by both PDHK2 and PDHK4. PMID:22360721

  3. The relationship between ethanol-induced hyperglycemia and hypothermia: evidence of genetic correlation.

    PubMed

    Risinger, F O; Cunningham, C L

    1991-08-01

    The hyperglycemic and hypothermic responses to acute ethanol exposure (0, 2, 4, 6 g/kg, intraperitoneally) were examined in non-fasted mice selectively bred for sensitivity (COLD line) or insensitivity (HOT line) to ethanol-induced hypothermia. Blood samples and rectal temperatures were obtained immediately before injection and hourly for 4 hr after injection. As expected, COLD mice demonstrated greater and more prolonged reductions in body temperature than HOT mice, especially at the 4 g/kg dose (HOT: -2.58 degrees C, COLD: -5.08 degrees C). Ethanol produced significant dose-dependent elevations in blood glucose levels over the 4-hr sampling period in both lines. The greatest elevations in blood glucose levels were seen at 4 g/kg, with COLD mice (mean = 225.1 mg/dl) showing significantly greater elevations in blood glucose levels compared to HOT mice (mean = 177.0 mg/dl). These results support the hypothesis that the thermic and glycemic effects produced by ethanol are due to related neural processes that share a common genetic component. PMID:1928651

  4. The effect of alpha-interferon, cyclosporine A, and radiation-induced immune suppression on morphine-induced hypothermia and tolerance.

    PubMed

    Dougherty, P M; Harper, C; Dafny, N

    1986-12-01

    An interconnection between the immune and the central nervous systems has been suggested by investigators studying the actions of several types of immune modifying agents and procedures upon opiate related phenomena. These studies have included the effects of altering immune system function by administration of either alpha-interferon, cyclosporine or radiation exposure upon naloxone-precipitated opiate withdrawal and upon opioid antinociceptive effects. The present study extends these earlier investigations by examining the effect of immune modulation upon opiate induced hypothermia. The results demonstrate that interferon and cyclosporine have no effects on baseline temperature or morphine induced hypothermia, while irradiation exposure elicits hyperthermia without affecting morphine-induced hypothermia. Finally, neither cyclosporine nor irradiation affect the development of tolerance to morphine induced hypothermia, while a single injection of the immune system modifier interferon was able to prevent the development of such tolerance. These observations suggest that yet another opiate-related phenomenon may be regulated at least in part by the immune system. These results together with our previous findings are further evidence of a link between the immune system and the CNS mediated through the opioid system. In addition, these studies further support our earlier hypothesis that "Interferon" is one of the endogenous substances which serves to prevent the development of tolerance and dependence to endogenous opioids. PMID:3784774

  5. Hypothermia followed by rapid rewarming exacerbates ischemia-induced brain injury and augments inflammatory response in rats.

    PubMed

    Zhu, Shu-Zhen; Gu, Yong; Wu, Zhou; Hu, Ya-Fang; Pan, Su-Yue

    2016-05-20

    Hypothermia followed by slow rewarming is neuroprotective for ischemic stroke. However, slow rewarming causes patients' longer stay in intensive care unit and increases the risk of hypothermic complications. Hypothermia followed by rapid rewarming (HTRR) is more convenient; but it exacerbates intracranial hypertension for patients with massive hemispheric infarcts. The present study aims to investigate in detail how HTRR exacerbates ischemic brain injury and what are underlying mechanisms. Rats subjected to transient focal ischemia by middle cerebral artery occlusion were treated with normothermia or hypothermia followed by rapid rewarming. Neurological outcome, neuronal injury, blood-brain barrier integrity and expressions of inflammatory cytokines were observed. Results showed that HTRR at a rate of 3 °C/20 min increased both neurological deficit score and Longa score, enhanced the loss of neurons and the plasma level of neuron-specific enolase. Rapid rewarmed rats also displayed increased Evans blue dye extravasation, matrix metalloproteinase 9 level and tight junction impairment. Meanwhile, interleukin-1β, -6, tumor necrosis factor α and cyclooxygenase-2 were markedly elevated in rapid rewarmed rats. Anti-inflammatory agent minocycline suppressed HTRR-induced elevation of inflammatory cytokines and improved neurological outcome. These results indicated that HTRR significantly impaired neurovascular unit and augmented proinflammatory response in stroke. PMID:27107700

  6. Regulated hypothermia in the hypothyroid rat induced by administration of propylthiouracil.

    PubMed

    Yang, Y; Gordon, C J

    1997-05-01

    Propylthiouracil (PTU), an antithyroidal drug that reduces serum L-thyroxine (T4) and 3,5,3'-triiodothyronine (T3), is presumed to lower core temperature (T0) by impairing metabolic thermogenesis. However, it is not understood why PTU-treated animals cannot use behavioral and other thermoeffectors to maintain normal Tc. Male rats were administered PTU in drinking water (0.05 mg/ml) while the following parameters were measured: 1) Tc and motor activity (MA) recorded by radiotelemetry for 24 h at ambient temperatures (Ta) of 10-30 degrees C; 2) selected Ta, MA, and Tc in a temperature gradient; and 3) Tc, MA, and grooming behavior during exposure to heat stress (TH = 34.5 degrees C) for 2 h. PTU reduced serum levels of T4, and T3 by 95 and 60%, respectively. Tc decreased after 3 days of PTU treatment; a 0.5 degree C decrease in Tc persisted throughout the PTU treatment. PTU rats exposed to Ta of 10-30 degrees C maintained a consistent hypothermic Tc during the light phase; however, a deficit in the stability of Tc at night was noted during exposure to 10 degrees C. In the temperature gradient, PTU rats selected warmer Ta, but their Tc was maintained at the same hypothermic levels as observed at fixed Ta values of 15-30 degrees C. Heat stress caused Tc of control rats to increase to 39 degrees C, whereas Tc of the PTU rats was maintained below 38 degrees C. The regulation of Tc at hypothermic levels over a wide range of Ta values and when rats were housed in a temperature gradient indicates that chronic PTU induces a state of regulated hypothermia. PMID:9176328

  7. Handling Hypothermia.

    ERIC Educational Resources Information Center

    Saho, S. Bamba

    1996-01-01

    Presents a unit on the body's response to hypothermia. Includes activities in which students measure the amount of heat absorbed by a white piece of cloth and a black piece of the same material, use cooperative-learning techniques to design a graphic organizer that explains metabolic responses to cold stress, and study the effect of temperature on…

  8. 5′-Adenosine Monophosphate-Induced Hypothermia Attenuates Brain Ischemia/Reperfusion Injury in a Rat Model by Inhibiting the Inflammatory Response

    PubMed Central

    Miao, Yi-Feng; Wu, Hui; Yang, Shao-Feng; Dai, Jiong; Qiu, Yong-Ming; Tao, Zhen-Yi; Zhang, Xiao-Hua

    2015-01-01

    Hypothermia treatment is a promising therapeutic strategy for brain injury. We previously demonstrated that 5′-adenosine monophosphate (5′-AMP), a ribonucleic acid nucleotide, produces reversible deep hypothermia in rats when the ambient temperature is appropriately controlled. Thus, we hypothesized that 5′-AMP-induced hypothermia (AIH) may attenuate brain ischemia/reperfusion injury. Transient cerebral ischemia was induced by using the middle cerebral artery occlusion (MCAO) model in rats. Rats that underwent AIH treatment exhibited a significant reduction in neutrophil elastase infiltration into neuronal cells and matrix metalloproteinase 9 (MMP-9), interleukin-1 receptor (IL-1R), tumor necrosis factor receptor (TNFR), and Toll-like receptor (TLR) protein expression in the infarcted area compared to euthermic controls. AIH treatment also decreased the number of terminal deoxynucleotidyl transferase dUTP nick end labeling- (TUNEL-) positive neuronal cells. The overall infarct volume was significantly smaller in AIH-treated rats, and neurological function was improved. By contrast, rats with ischemic brain injury that were administered 5′-AMP without inducing hypothermia had ischemia/reperfusion injuries similar to those in euthermic controls. Thus, the neuroprotective effects of AIH were primarily related to hypothermia. PMID:25873763

  9. Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

    SciTech Connect

    Chan, Ming-Huan; Chung, Shiang-Sheng; Stoker, Astrid K.; Markou, Athina; Chen, Hwei-Hsien

    2012-12-01

    Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDA receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene-induced

  10. Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model

    PubMed Central

    Horst, K.; Eschbach, D.; Pfeifer, R.; Relja, B.; Sassen, M.; Steinfeldt, T.; Wulf, H.; Vogt, N.; Frink, M.; Ruchholtz, S.; Pape, H. C.; Hildebrand, F.

    2016-01-01

    Background Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma. Materials & Methods Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min). After resuscitation, hypothermia (33°C) was induced for a period of 12 h (HT-T group) with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA. Results Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h. Conclusion A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application. PMID:27144532

  11. Cannabidiol fails to reverse hypothermia or locomotor suppression induced by Ù9-tetrahydrocannabinol in Sprague-Dawley rats

    PubMed Central

    Taffe, Michael A; Creehan, Kevin M; Vandewater, Sophia A

    2015-01-01

    Background and Purpose Growing evidence shows cannabidiol (CBD) modulates some of the effects of Δ9-tetrahydrocannabinol (THC). CBD is a constituent of some strains of recreational cannabis but its content is highly variable. High CBD strains may have less memory-impairing effects than low-CBD strains and CBD can reverse behavioural effects of THC in monkeys. CBD/THC interactions in rodents are more complicated as CBD can attenuate or exacerbate the effects of THC. This study was undertaken to determine if CBD could reverse hypothermia or hypolocomotor effects caused by THC in rats. Experimental Approaches Male Sprague-Dawley rats were prepared with radiotelemetry devices and then given doses of THC (10–30 mg·kg−1, i.p.) with or without CBD. Experiments determined the effect of simultaneous or 30 min pretreatment with CBD in a 1:1 ratio with THC, as well as the effect of CBD in a 3:1 ratio. Additional experiments determined the effects of pretreatment with the cannabinoid CB1 receptor antagonist SR141716 (rimonabant). Key Results CBD did not attentuate THC-induced hypothermia or hypolocomotion but instead exaggerated these effects in some conditions. The antagonist SR141716 blocked hypolocomotor effects of THC for the first hour after injection and the hypothermia for 6 h; thus validating the pharmacological model. Conclusions and Implications There is no evidence from this study that elevated CBD content in cannabis could provide protection from the physiological effects of THC, in rats. PMID:25425111

  12. Utilization of Hyperbaric Oxygen Therapy and Induced Hypothermia After Hydrogen Sulfide Exposure

    PubMed Central

    Asif, Mir J.; Exline, Matthew C.

    2013-01-01

    Hydrogen sulfide is a toxic gas produced as a byproduct of organic waste and many industrial processes. Hydrogen sulfide exposure symptoms may vary from mild (dizziness, headaches, nausea) to severe lactic acidosis via its inhibition of oxidative phosphorylation, leading to cardiac arrhythmias and death. Treatment is generally supportive. We report the case of a patient presenting with cardiac arrest secondary to hydrogen sulfide exposure treated with both hyperbaric oxygen therapy and therapeutic hypothermia with great improvement in neurologic function. PMID:22004989

  13. Prolonged induced hypothermia in hemorrhagic shock is associated with decreased muscle metabolism: a nuclear magnetic resonance-based metabolomics study.

    PubMed

    Lusczek, Elizabeth R; Lexcen, Daniel R; Witowski, Nancy E; Determan, Charles; Mulier, Kristine E; Beilman, Greg

    2014-01-01

    Hemorrhagic shock is a leading cause of trauma-related death in war and is associated with significant alterations in metabolism. Using archived serum samples from a previous study, the purpose of this work was to identify metabolic changes associated with induced hypothermia in a porcine model of hemorrhagic shock. Twelve Yorkshire pigs underwent a standardized hemorrhagic shock and resuscitation protocol to simulate battlefield injury with prolonged evacuation to definitive care in cold environments. Animals were randomized to receive either hypothermic (33°C) or normothermic (39°C) limited resuscitation for 8 h, followed by standard resuscitation. Proton nuclear magnetic resonance spectroscopy was used to evaluate serum metabolites from these animals at intervals throughout the hypothermic resuscitation period. Animals in the hypothermic group had a significantly higher survival rate (P = 0.02) than normothermic animals. Using random forest analysis, a difference in metabolic response between hypothermic and normothermic animals was identified. Hypothermic resuscitation was characterized by decreased concentrations of several muscle-related metabolites including taurine, creatine, creatinine, and amino acids. This study suggests that a decrease in muscle metabolism as a result of induced hypothermia is associated with improved survival. PMID:24052038

  14. Neuroprotective effect of preoperatively induced mild hypothermia as determined by biomarkers and histopathological estimation in a rat subdural hematoma decompression model

    PubMed Central

    Yokobori, Shoji; Gajavelli, Shyam; Mondello, Stefania; Mo-Seaney, Jixiang; Hayes, Ronald L; Bramlett, Helen M.; Dietrich, W. Dalton; Bullock, M. Ross

    2016-01-01

    Object In traumatic brain injury (TBI) patients, hypothermia therapy has not shown efficacy in multicenter clinical trials. With the post-hoc data from the latest clinical trial (NABIS:H II), we hypothesized that hypothermia may be beneficial in the rat acute subdural hematoma (ASDH) model by blunting the effects of ischemic/ reperfusional (I/R) injury. The major aim of our study was to test the efficacy of temperature management in reducing brain damage after ASDH. Methods Rats were induced with ASDH and placed into (1) Normothermia group (37°C) (2) Early hypothermia group; head and body temperature reduced to 33°C at 30 minutes prior to craniotomy (3) Late hypothermia group; temperature was lowered to 33°C at 30 minutes after decompression (4) Sham group; no ASDH and underwent only craniotomy with normothermia. To assess of neuronal and glial cell damage, we analyzed microdialysate (MD ; using 100kD probe) concentrations of: glial fibrillary acidic protein (GFAP) and ubiquitin carboxyl-terminal hydrolase-L1 (UCH-L1). Fluoro-Jade B (FJB) positive neurons and injury volume with 2,3,5-triphenyltetrazolium chloride (TTC) staining were also measured. Results In the early phase of reperfusion (30min- 2.5 hrs after decompression), extracellular UCH-L1 in the early hypothermia group was significantly lower than in the normothermia. (Early; 4.9±1.0 ng/dl, Late; 35.2±12.1 ng/dl, Normo; 50.20± 28.3 ng/dl, Sham; 3.1±1.3 ng/dl, Early vs Normo; p < 0.01, Sham vs Normo; p < 0.01, analyzed with ANOVA followed by a post-hoc Bonferroni’s test ). In the late phase of reperfusion (> 2.5hrs after decompression), extracellular GFAP in the early hypothermia group was also lower than in the normothermia and late hypothermia groups (Early; 5.5±2.9 ng/dl, Late; 7.4±3.4 ng/dl, Normo; 15.3±8.4 ng/dl, Sham; 3.3±1.0 ng/dl, Normo vs Sham; p < 0.01). The number of FJB positive cells in early hypothermia group was significantly smaller than in normothermia group (Normo vs Early: 774

  15. Fructose 1,6 biphosphate administration to rats prevents metabolic acidosis and oxidative stress induced by deep hypothermia and rewarming.

    PubMed

    Alva, Norma; Carbonell, Teresa; Roig, Teresa; Bermúdez, Jordi; Palomeque, Jesús

    2011-06-01

    Fructose 1,6 biphosphate (F1,6BP) exerts a protective effect in several in vitro models of induced injury and in isolated organs; however, few studies have been performed using in vivo hypothermia. Here we studied the effects of deep hypothermia (21ºC) and rewarming in anaesthetised rats after F1,6BP administration (2 g/kg body weight). Acid-base and oxidative stress parameters (plasma malondialdehyde and glutathione, and erythrocyte antioxidant enzymes) were evaluated. Erythrocyte and leukocyte numbers in blood and plasma nitric oxide were also measured 3 h after F1,6BP administration in normothermia animals. In the absence of F1,6BP metabolic acidosis developed after rewarming. Oxidative stress was also evident after rewarming, as shown by a decrease in thiol groups and in erythrocyte superoxide dismutase, catalase and GSH-peroxidase, which corresponded to an increase in AST in rewarmed animals. These effects were reverted in rats treated with F1,6BP. Blood samples of F1,6BP-treated animals showed a significant increase in plasma nitric oxide 3 h after administration, coinciding with a significant rise in leukocyte number. F1,6BP protection may be due to the decrease in oxidative stress and to the preservation of the antioxidant pool. In addition, we propose that the reduction in extracellular acidosis may be due to improved tissue perfusion during rewarming and that nitric oxide may play a central role. PMID:21463624

  16. Beneficial effects of fructose 1,6-biphosphate on hypothermia-induced reactive oxygen species injury in rats.

    PubMed

    Gámez, Antonio; Alva, Norma; Roig, Teresa; Bermúdez, Jordi; Carbonell, Teresa

    2008-08-20

    The release of reactive oxygen species has been described in hypothermic cells and tissues. Fructose 1,6-biphosphate (F1,6-BP) protects tissue stored at cold temperatures. We study the effect of F1,6-BP in vivo administration on anaesthetized rats exposed to cold stress (4 degrees C chamber for 30 min) and rewarming, to see if it alters cold-induced oxidative injury. Body temperatures show that the animals reached moderate hypothermia (26.80+/-0.62 degrees C) after 30 min of cold exposition. A decrease in mean arterial pressure was found. One group of animals was then rewarmed. Both hypothermia and rewarming increased the production of thiobarbituric acid-reactive substances, an index of lipid peroxidation, and reduced the antioxidant levels of plasmatic sulfhydryl groups, as well as decreasing the enzymatic activities of Cu,Zn-superoxide dismutase (Cu,Zn-SOD), catalase and GSH peroxidase in erythrocytes. Administration of F1,6-BP increased sulfhydryl groups and limited lipid peroxidation in plasma. It furthermore enhanced Cu,Zn-SOD and GSH peroxidase antioxidant activity in erythrocytes and preserved mean arterial pressure. Therefore, F1,6-BP has therapeutic potential based on its ability to reduce free-radical injury resulting from acute cold exposure and rewarming in vivo. PMID:18602097

  17. Mild hypothermia causes differential, time-dependent changes in cytokine expression and gliosis following endothelin-1-induced transient focal cerebral ischemia

    PubMed Central

    2011-01-01

    Background Stroke is an important cause of morbidity and mortality and few therapies exist thus far. Mild hypothermia (33°C) is a promising neuroprotective strategy to improve outcome after ischemic stroke. However, its complete mechanism of action has not yet been fully elaborated. This study is the first to investigate whether this neuroprotection occurs through modulation of the neuroinflammatory response after stroke in a time-dependent manner. Methods The Endothelin-1 (Et-1) model was used to elicit a transient focal cerebral ischemia in male Wistar rats. In this model, the core and penumbra of the insult are represented by the striatum and the cortex respectively. We assessed the effects of 2 hours of hypothermia, started 20 minutes after Et-1 injection on neurological outcome and infarct volume. Furthermore, pro- and anti-inflammatory cytokine expression was determined using ELISA. Microgliosis and astrogliosis were investigated using CD-68 and GFAP staining respectively. All parameters were determined 8, 24, 72 hours and 1 week after the administration of Et-1. Results Et-1 infusion caused neurological deficit and a reproducible infarct size which increased up to 3 days after the insult. Both parameters were significantly reduced by hypothermia. The strongest reduction in infarct volume with hypothermia, at 3 days, corresponded with increased microglial activation. Reducing the brain temperature affected the stroke induced increase in interleukin-1β and tumor necrosis factor α in the striatum, 8 hours after its induction, but not at later time points. Transforming growth factor β increased as a function of time after the Et-1-induced insult and was not influenced by cooling. Hypothermia reduced astrogliosis at 1 and 3 days after stroke onset. Conclusions The beneficial effects of hypothermia after stroke on infarct volume and functional outcome coincide with a time-dependent modulation of the cytokine expression and gliosis. PMID:21627837

  18. Hypothermia protects against oxygen-glucose deprivation-induced neuronal injury by down-regulating the reverse transport of glutamate by astrocytes as mediated by neurons.

    PubMed

    Wang, D; Zhao, Y; Zhang, Y; Zhang, T; Shang, X; Wang, J; Liu, Y; Kong, Q; Sun, B; Mu, L; Liu, X; Wang, G; Li, H

    2013-05-01

    Glutamate is the major mediator of excitotoxic neuronal death following cerebral ischemia. Under severe ischemic conditions, glutamate transporters can functionally reverse to release glutamate, thereby inducing further neuronal injury. Hypothermia has been shown to protect neurons from brain ischemia. However, the mechanism(s) involved remain unclear. Therefore, the aim of this study was to investigate the mechanism(s) mediating glutamate release during brain ischemia-reperfusion injury under hypothermic conditions. Neuron/astrocyte co-cultures were exposed to oxygen-glucose deprivation (OGD) at various temperatures for 2h, and cell viability was assayed 12h after reoxygenation. PI and MAP-2 staining demonstrated that hypothermia significantly decreased neuronal injury. Furthermore, [(3)H]-glutamate uptake assays showed that hypothermia protected rat primary cortical cultures against OGD reoxygenation-induced injury. Protein levels of the astrocytic glutamate transporter, GLT-1, which is primarily responsible for the clearance of extracellular glutamate, were also found to be reduced in a temperature-dependent manner. In contrast, expression of GLT-1 in astrocyte-enriched cultures was found to significantly increase following the addition of neuron-conditioned medium maintained at 37 °C, and to a lesser extent with neuron-conditioned medium at 33 °C. In conclusion, the neuroprotective effects of hypothermia against brain ischemia-reperfusion injury involve down-regulation of astrocytic GLT-1, which mediates the reverse transport of glutamate. Moreover, this process may be regulated by molecules secreted by stressed neurons. PMID:23402854

  19. Veno-venous extracorporeal blood shunt cooling to induce mild hypothermia in dog experiments and review of cooling methods.

    PubMed

    Behringer, Wilhelm; Safar, Peter; Wu, Xianren; Nozari, Ala; Abdullah, Ali; Stezoski, S William; Tisherman, Samuel A

    2002-07-01

    Mild hypothermia (33-36 degrees C) might be beneficial when induced during or after insults to the brain (cardiac arrest, brain trauma, stroke), spinal cord (trauma), heart (acute myocardial infarction), or viscera (hemorrhagic shock). Reaching the target temperature rapidly in patients inside and outside hospitals remains a challenge. This study was to test the feasibility of veno-venous extracorporeal blood cooling for the rapid induction of mild hypothermia in dogs, using a simple pumping-cooling device. Ten custom-bred hunting dogs (21-28 kg) were lightly anesthetized and mechanically ventilated. In five dogs, two catheters were inserted through femoral veins, one peripheral and the other into the inferior vena cava. The catheters were connected via a coiled plastic tube as heat exchanger (15 m long, 3 mm inside diameter, 120 ml priming volume), which was immersed in an ice-water bath. A small roller-pump produced a veno-venous flow of 200 ml/min (about 10% of cardiac output). In five additional dogs (control group), a clinically practiced external cooling method was employed, using alcohol over the skin of the trunk and fanning plus ice-bags. During spontaneous normotension, veno-venous cooling delivered blood into the vena cava at 6.2 degrees C standard deviation (SD 1.4) and decreased tympanic membrane (Tty) temperature from 37.5 to 34.0 degrees C at 5.2 min (SD 0.7), and to 32.0 degrees C at 7.9 min (SD 1.3). Skin surface cooling decreased tympanic temperature from 37.5 to 34.0 degrees C at 19.9 min (SD 3.7), and to 32.0 degrees C at 29.9 (SD 5.1) (P=0.001). Heart rates at Tty 34 and 32 degrees C were significantly lower than at baseline in both groups, but within physiological range, without difference between groups. There were no arrhythmias. We conclude that in large dogs the induction of mild systemic hypothermia with extracorporeal veno-venous blood shunt cooling is simple and four times more rapid than skin surface cooling. PMID:12104113

  20. What is Hypothermia?

    MedlinePlus

    ... Weather! Heath and Aging Stay Safe in Cold Weather! What is hypothermia? If you are like most ... Keep warm inside Related Publications Hypothermia: A Cold Weather Hazard There's No Place Like Home - For Growing ...

  1. Hibernation, Hypothermia and a Possible Therapeutic “Shifted Homeostasis” Induced by Central Activation of A1 Adenosine Receptor (A1AR)*

    PubMed Central

    Tupone, Domenico; Cetas, Justin S.; Morrison, Shaun F.

    2016-01-01

    The positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Pharmacological manipulation of central autonomic thermoregulatory circuits could represent a potential target for the induction of a hypothermic state. Here we present a brief description of the CNS thermoregulatory centers and how the manipulation of these circuits can be useful in the treatment of pathological conditions such as stroke or brain hemorrhage. PMID:27333659

  2. Chronic Cold-Water-Induced Hypothermia Impairs Memory Retrieval and Nepeta menthoides as a Traditional "Hot" Herb Reverses the Impairment.

    PubMed

    Ahmadian-Attar, Mohammad Mahdi; Ahmadiani, Abolhassan; Kamalinejad, Mohammad; Dargahi, Leila; Mosaddegh, Mahmoud

    2014-01-01

    Iranian Traditional Medicine (ITM) describes a kind of dementia with similar signs and symptoms of Alzheimer's disease (AD). It explains the pathology of dementia with cold intemperament of the brain, which means that the brain is colder than its healthy form. ITM strategy for treatment of dementia is to heat the brain up by medical "hot" herbs. Nepeta menthoides (NM) is one of these "hot" herbs. To evaluate the veracity of ITM concept about dementia and its treatment, we first try to examine if coldness of brain can make memory impairment. If so, can NM reverse memory impairment? Rats in cold-water-induced hypothermic (CWH) groups were immersed up to the neck in 3.5 °C water, for 5 min during 14 consecutive days. As a control, rats were forced to swim in warm water at the same conditions. To eliminate the impact of forced swimming stress, a group of intact rats was also added. After last swimming in day 14, some groups received drug (100 or 500 mg/ Kg aqueous extract of NM) or vehicle via i.p. injection. Learning and memory were assessed by Morris water maze, and tau hyperphosphorylation was measured by western blotting. The results showed that CWH impairs learning and memory and induces tau hyperphosphorylation. 100 mg/Kg of NM reversed memory impairment as well as tau hyperphosphorylation. ITM theory about the relationship between brain hypothermia and dementia is in accordance with our findings. PMID:24711845

  3. Guideline Implementation: Preventing Hypothermia.

    PubMed

    Bashaw, Marie A

    2016-03-01

    The updated AORN "Guideline for prevention of unplanned patient hypothermia" provides guidance for identifying factors associated with intraoperative hypothermia, preventing hypothermia, educating perioperative personnel on this topic, and developing relevant policies and procedures. This article focuses on key points of the guideline, which addresses performing a preoperative assessment for factors that may contribute to hypothermia, measuring and monitoring the patient's temperature in all phases of perioperative care, and implementing interventions to prevent hypothermia. Perioperative RNs should review the complete guideline for additional information and for guidance when writing and updating policies and procedures. PMID:26924369

  4. Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study

    PubMed Central

    Hoedemaekers, Cornelia W; Ezzahti, Mustapha; Gerritsen, Aico; van der Hoeven, Johannes G

    2007-01-01

    Background Temperature management is used with increased frequency as a tool to mitigate neurological injury. Although frequently used, little is known about the optimal cooling methods for inducing and maintaining controlled normo- and hypothermia in the intensive care unit (ICU). In this study we compared the efficacy of several commercially available cooling devices for temperature management in ICU patients with various types of neurological injury. Methods Fifty adult ICU patients with an indication for controlled mild hypothermia or strict normothermia were prospectively enrolled. Ten patients in each group were assigned in consecutive order to conventional cooling (that is, rapid infusion of 30 ml/kg cold fluids, ice and/or coldpacks), cooling with water circulating blankets, air circulating blankets, water circulating gel-coated pads and an intravascular heat exchange system. In all patients the speed of cooling (expressed as°C/h) was measured. After the target temperature was reached, we measured the percentage of time the patient's temperature was 0.2°C below or above the target range. Rates of temperature decline over time were analyzed with one-way analysis of variance. Differences between groups were analyzed with one-way analysis of variance, with Bonferroni correction for multiple comparisons. A p < 0.05 was considered statistically significant. Results Temperature decline was significantly higher with the water-circulating blankets (1.33 ± 0.63°C/h), gel-pads (1.04 ± 0.14°C/h) and intravascular cooling (1.46 ± 0.42°C/h) compared to conventional cooling (0.31 ± 0.23°C/h) and the air-circulating blankets (0.18 ± 0.2°C/h) (p < 0.01). After the target temperature was reached, the intravascular cooling device was 11.2 ± 18.7% of the time out of range, which was significantly less compared to all other methods. Conclusion Cooling with water-circulating blankets, gel-pads and intravascular cooling is more efficient compared to conventional

  5. Unintended Perioperative Hypothermia

    PubMed Central

    Hart, Stuart R.; Bordes, Brianne; Hart, Jennifer; Corsino, Daniel; Harmon, Donald

    2011-01-01

    Background Hypothermia, defined as a core body temperature less than 36°C (96.8°F), is a relatively common occurrence in the unwarmed surgical patient. A mild degree of perioperative hypothermia can be associated with significant morbidity and mortality. A threefold increase in the frequency of surgical site infections is reported in colorectal surgery patients who experience perioperative hypothermia. As part of the Surgical Care Improvement Project, guidelines aim to decrease the incidence of this complication. Methods We review the physiology of temperature regulation, mechanisms of hypothermia, effects of anesthetics on thermoregulation, and consequences of hypothermia and summarize recent recommendations for maintaining perioperative normothermia. Results Evidence suggests that prewarming for a minimum of 30 minutes may reduce the risk of subsequent hypothermia. Conclusions Monitoring of body temperature and avoidance of unintended perioperative hypothermia through active and passive warming measures are the keys to preventing its complications. PMID:21960760

  6. Impairment of Rat Spatial Learning and Memory in a New Model of Cold Water-Induced Chronic Hypothermia: Implication for Alzheimer's Disease.

    PubMed

    Ahmadian-Attari, Mohammad Mahdi; Dargahi, Leila; Mosaddegh, Mahmoud; Kamalinejad, Mohammad; Khallaghi, Behzad; Noorbala, Fatemeh; Ahmadiani, Abolhassan

    2015-08-01

    Alzheimer's disease (AD) is a primary neurodegenerative disorder associated with progressive memory impairment. Recent studies suggest that hypothermia may contribute to the development and exacerbation of AD. The aim of this study was to investigate the role of chronic hypothermia on spatial learning and memory performance as well as brain immunohistochemical (IHC) and molecular changes. Four groups of male rats were placed in cold water (3.5 ± 0.5 °C) once a day for 1, 3, 6, and 14 days, four other groups were placed in warm water (32 °C) as the control groups to eliminate the effect of swimming stress, and one more group which comprised intact animals that were kept in a normothermic situation and had no swimming stress. Twenty-four hours after the last intervention, spatial learning and memory were assessed, using the modified Morris water maze. After the behavioral test, the rats' brains were removed for IHC and Western blotting. The results showed that memory retrieval is impaired after 14 days of cold water-induced hypothermia (CWH) (P < 0.05). IHC showed the formation of beta-amyloid plaques after a 14-day CWH. The molecular changes demonstrated that a 14-day CWH induces tau hyperphosphorylation, apoptosis, and reduces COX-II expression. Therefore, chronic CWH, independent of forced swimming stress, impairs learning and memory through molecular mechanisms similar to those of AD. In conclusion, CWH may serve as an important model to assess the role of hypothermia in AD pathogenesis. PMID:25782579

  7. 2-Deoxy-D-glucose-induced hypothermia in anesthetized rats: Lack of forebrain contribution and critical involvement of the rostral raphe/parapyramidal regions of the medulla oblongata.

    PubMed

    Osaka, Toshimasa

    2015-07-01

    Systemic or central administration of 2-deoxy-d-glucose (2DG), a competitive inhibitor of glucose utilization, induces hypothermia in awake animals and humans. This response is mediated by the central nervous system, though the neural mechanism involved is largely unknown. In this study, I examined possible involvement of the forebrain, which contains the hypothalamic thermoregulatory center, and the medullary rostral raphe/parapyramidal regions (rRPa/PPy), which mediate hypoxia-induced heat-loss responses, in 2DG-induced hypothermia in urethane-chloralose-anesthetized, neuromuscularly blocked, artificially ventilated rats. The intravenous injection of 2DG (250mgkg(-1)) elicited an increase in tail skin temperature and decreases in body core temperature and the respiratory exchange ratio, though it did not induce any significant change in the metabolic rate. These results indicate that the hypothermic response was caused by an increase in heat loss, but not by a decrease in heat production and that it was accompanied by a decrease in carbohydrate utilization and/or an increase in lipid utilization as energy substrates. Complete surgical transection of the brainstem between the hypothalamus and the midbrain had no effect on the 2DG-induced hypothermic responses, suggesting that the hindbrain, but not the forebrain, was sufficient for the responses. However, pretreatment of the rRPa/PPy with the GABAA receptor blocker bicuculline methiodide, but not with vehicle saline, greatly attenuated the 2DG-induced responses, suggesting that the 2DG-induced hypothermia was mediated, at least in part, by GABAergic neurons in the hindbrain and activation of GABAA receptors on cutaneous sympathetic premotor neurons in the rRPa/PPy. PMID:26146232

  8. Modeling drug- and system-related changes in body temperature: application to clomethiazole-induced hypothermia, long-lasting tolerance development, and circadian rhythm in rats.

    PubMed

    Visser, Sandra A G; Sällström, Björn; Forsberg, Tomas; Peletier, Lambertus A; Gabrielsson, Johan

    2006-04-01

    The aim of the present investigation was to develop a pharmacokinetic-pharmacodynamic model for the characterization of clomethiazole (CMZ)-induced hypothermia and the rapid development of long-lasting tolerance in rats while taking into account circadian rhythm in baseline and the influence of handling. CMZ-induced hypothermia and tolerance was measured using body temperature telemetry in male Sprague-Dawley rats, which were given s.c. bolus injections of 0, 15, 150, 300, and 600 micromol kg(-1) and 24-h s.c. continuous infusions of 0, 20, and 40 micromol kg(-1) h(-1) using osmotic pumps. The duration of tolerance was studied by repeated injections of 300 micromol kg(-1) at 3- to 32-day intervals. Plasma exposure to CMZ was obtained in satellite groups of catheterized rats. Fitted population concentration-time profiles served as input for the pharmacodynamic analysis. The asymmetric circadian rhythm in baseline body temperature was successfully described by a novel negative feedback model incorporating external light-dark conditions. An empirical function characterized the transient increase in temperature upon handling of the animal. A feedback model for temperature regulation and tolerance development allowed estimation of CMZ potency at 30 +/- 1 microM. The delay in onset of tolerance was estimated via a series of four transit compartments at 7.6 +/- 2 h. The long-lasting tolerance was assumed to be caused by inactivation of a mediator with an estimated turnover time of 46 +/- 3 days. This multicomponent turnover model was able to quantify the CMZ-induced hypothermia, circadian rhythm in baseline, and rapid onset of a long-lasting tolerance to CMZ in rats. PMID:16339393

  9. Oxidative Stress and Antioxidant Activity in Hypothermia and Rewarming: Can RONS Modulate the Beneficial Effects of Therapeutic Hypothermia?

    PubMed Central

    Alva, Norma; Palomeque, Jesús

    2013-01-01

    Hypothermia is a condition in which core temperature drops below the level necessary to maintain bodily functions. The decrease in temperature may disrupt some physiological systems of the body, including alterations in microcirculation and reduction of oxygen supply to tissues. The lack of oxygen can induce the generation of reactive oxygen and nitrogen free radicals (RONS), followed by oxidative stress, and finally, apoptosis and/or necrosis. Furthermore, since the hypothermia is inevitably followed by a rewarming process, we should also consider its effects. Despite hypothermia and rewarming inducing injury, many benefits of hypothermia have been demonstrated when used to preserve brain, cardiac, hepatic, and intestinal function against ischemic injury. This review gives an overview of the effects of hypothermia and rewarming on the oxidant/antioxidant balance and provides hypothesis for the role of reactive oxygen species in therapeutic hypothermia. PMID:24363826

  10. Ethanol-induced hypothermia and thermogenesis of brown adipose tissue in the rat.

    PubMed

    Huttunen, P; Sämpi, M; Myllylä, R

    1998-05-01

    The effects of two ethanol doses (2 and 3 g/kg) on colonic temperature and levels of norepinephrine (NE) and uncoupling protein (UCP) mRNA in the interscapular brown adipose tissue (IBAT) were examined in rats exposed to 20 degrees C or 4 degrees C for 2 h. The controls received 0.9% NaCl solution. Ethanol produced a significant hypothermic effect versus saline at both temperature conditions. The dose at 3 g/kg reduced colonic temperature more in the cold than at room temperature (p < 0.01), whereas the ambient temperature did not affect the decrease in rats that received ethanol 2 g/kg. At room temperature ethanol did not significantly change the levels of NE or UCP mRNA, whereas after cold exposure (4 degrees C) NE levels in the ethanol-treated rats were significantly lower than in the controls (p < 0.001). Ethanol did not prevent a cold-induced increase in the UCP mRNA levels, although it reduced an increase. The magnitude of the reduction in increase was dependent on the dose, being significant at the dose of 3 g/kg (p < 0.05). The results show that the ethanol-induced drop in body temperature is not necessarily related to IBAT thermogenesis, as indicated by the levels of NE and UCP mRNA. PMID:9590517

  11. Therapeutic Hypothermia for Neuroprotection

    PubMed Central

    Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

    2014-01-01

    The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known. PMID:24982721

  12. Hypothermia: A Cold Weather Hazard

    MedlinePlus

    ... Weather Hazard Heath and Aging Hypothermia: A Cold Weather Hazard What Are The Signs Of Hypothermia? Taking ... cold air. But, not everyone knows that cold weather can also lower the temperature inside your body. ...

  13. Rescue hypothermia for refractory hypercapnia.

    PubMed

    Pietrini, Domenico; Pennisi, Mariano; Vitale, Francesca; Pulitanò, Silvia Maria; Conti, Giorgio; Mancino, Aldo; Piastra, Marco; De Luca, Daniele

    2012-12-01

    Hypothermia may reduce the CO(2) production by decreasing the metabolism of the cooled tissue. We describe the first clinical use of hypothermia to lower hypercarbia in a case of bronchiolitis related respiratory failure unresponsive to maximal respiratory support. In this case, hypothermia allowed sparing the use of extracorporeal life support. Conclusion Hypothermia might be useful for severe acute respiratory failure unresponsive to aggressive respiratory support. PMID:22692802

  14. The effect of hypothermia on influx of leukocytes in the digital lamellae of horses with oligofructose-induced laminitis.

    PubMed

    Godman, Jennifer D; Burns, Teresa A; Kelly, Carlin S; Watts, Mauria R; Leise, Britta S; Schroeder, Eric L; van Eps, Andrew W; Belknap, James K

    2016-10-01

    Sepsis-related laminitis (SRL) is a common complication in the septic/endotoxemic critically-ill equine patient, in which lamellar injury and failure commonly lead to crippling distal displacement of the distal phalanx. Similar to organ injury in human sepsis, lamellar injury in SRL has been associated with inflammatory events, including the influx of leukocytes into the lamellar tissue and markedly increased expression of a wide array of inflammatory mediators at the onset of Obel grade 1 (OG1) laminitis. The only treatment reported both clinically and experimentally to protect the lamellae in SRL, local hypothermia ("cryotherapy"), has been demonstrated to effectively inhibit lamellar expression of multiple inflammatory mediators when initiated at the time of administration of a carbohydrate overload in experimental models of SRL. However, the effect of hypothermia on leukocyte influx into affected tissue has not been assessed. We hypothesized that cryotherapy inhibits leukocyte emigration into the digital lamellae in SRL. Immunohistochemical staining using leukocyte markers MAC387 (marker of neutrophils, activated monocytes) and CD163 (monocyte/macrophage-specific marker) was performed on archived lamellar tissue samples from an experimental model of SRL in which one forelimb was maintained at ambient temperature (AMB) and one forelimb was immersed in ice water (ICE) immediately following enteral oligofructose administration (10g/kg, n=14 horses). Lamellae were harvested at 24h post-oligofructose administration (DEV, n=7) or at the onset of OG1 laminitis (OG1, n=7). Both MAC387-positive and CD163-positive cells were counted by a single blinded investigator on images [n=10 (40× fields/digit for MAC387 and 20x fields/digit for CD163)] obtained using Aperio microscopy imaging analysis software. Data were assessed for normality and analyzed with a paired t-test and one-way ANOVA with significance set at p<0.05. MAC387-positive cells were present in low numbers in

  15. Hypothermia improves outcome from cardiac arrest.

    PubMed

    Bernard, S A

    2005-12-01

    Out-of-hospital cardiac arrest is common and patients who are initially resuscitated by ambulance officers and transported to hospital are usually admitted to the intensive care unit (ICU). In the past, the treatment in the ICU consisted of supportive care only, and most patients remained unconscious due to the severe anoxic neurological injury. It was this neurological injury rather than cardiac complications that caused the high rate of morbidity and mortality. However, in the early 1990's, a series of animal experiments demonstrated convincingly that mild hypothermia induced after return of spontaneous circulation and maintained for several hours dramatically reduced the severity of the anoxic neurological injury. In the mid-1990's, preliminary human studies suggested that mild hypothermia could be induced and maintained in post-cardiac arrest patients without an increase in the rate of cardiac or other complications. In the late 1990's, two prospective, randomised, controlled trials were conducted and the results confirmed the animal data that mild hypothermia induced after resuscitation and maintained for 12 - 24 hours dramatically improved neurological and overall outcomes. On the basis of these studies, mild hypothermia was endorsed in 2003 by the International Liaison Committee on Resuscitation as a recommended treatment for comatose patients with an initial cardiac rhythm of ventricular fibrillation. However, the application of this therapy into routine clinical critical care practice has been slow. The reasons for this are uncertain, but may relate to the relative complexity of the treatment, unfamiliarity with the pathophysiology of hypothermia, lack of clear protocols and/or uncertainty of benefit in particular patients. Therefore, recent research in this area has focused on the development of feasible, inexpensive techniques for the early, rapid induction of mild hypothermia after cardiac arrest. Currently, the most promising strategy is a rapid

  16. Transient Receptor Potential Channel Opening Releases Endogenous Acetylcholine, which Contributes to Endothelium-Dependent Relaxation Induced by Mild Hypothermia in Spontaneously Hypertensive Rat but Not Wistar-Kyoto Rat Arteries.

    PubMed

    Zou, Q; Leung, S W S; Vanhoutte, P M

    2015-08-01

    Mild hypothermia causes endothelium-dependent relaxations, which are reduced by the muscarinic receptor antagonist atropine. The present study investigated whether endothelial endogenous acetylcholine contributes to these relaxations. Aortic rings of spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto (WKY) rats were contracted with prostaglandin F2 α and exposed to progressive mild hypothermia (from 37 to 31°C). Hypothermia induced endothelium-dependent, Nω-nitro-l-arginine methyl ester-sensitive relaxations, which were reduced by atropine, but not by mecamylamine, in SHR but not in WKY rat aortae. The responses in SHR aortae were also reduced by acetylcholinesterase (the enzyme responsible for acetylcholine degradation), bromoacetylcholine (inhibitor of acetylcholine synthesis), hemicholinium-3 (inhibitor of choline uptake), and vesamicol (inhibitor of acetylcholine release). The mild hypothermia-induced relaxations in both SHR and WKY rat aortae were inhibited by AMTB [N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide; the transient receptor potential (TRP) M8 inhibitor]; only those in SHR aortae were inhibited by HC-067047 [2-methyl-1-[3-(4-morpholinyl)propyl]-5-phenyl-N-[3-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide; TRPV4 antagonist] while those in WKY rat aortae were reduced by HC-030031 [2-(1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl)-N-(4-isopropylphenyl)acetamide; TRPA1 antagonist]. The endothelial uptake of extracellular choline and release of cyclic guanosine monophosphate was enhanced by mild hypothermia and inhibited by HC-067047 in SHR but not in WKY rat aortae. Compared with WKY rats, the SHR preparations expressed similar levels of acetylcholinesterase and choline acetyltransferase, but a lesser amount of vesicular acetylcholine transporter, located mainly in the endothelium. Thus, mild hypothermia causes nitric oxide-dependent relaxations by opening TRPA1 channels in WKY rat aortae

  17. Effects of therapeutic hypothermia on the glial proteome and phenotype.

    PubMed

    Kim, Jong-Heon; Seo, Minchul; Suk, Kyoungho

    2013-02-01

    Therapeutic hypothermia is a useful intervention against brain injury in experimental models and patients, but its therapeutic applications are limited due to its ill-defined mode of action. Glia cells maintain homeostasis and protect the central nervous system from environmental change, but after brain injury, glia are activated and induce glial scar formation and secondary injury. On the other hand, therapeutic hypothermia has been shown to modulate glial hyperactivation under various brain injury conditions. We considered that knowledge of the effect of hypothermia on the molecular profiles of glia and on their phenotypes would improve our understanding of the neuroprotective mechanism of hypothermia. Here, we review the findings of recent studies that examined the effect of hypothermia on proteome changes in reactive glial cells in vitro and in vivo. The therapeutic effects of hypothermia are associated with the inhibition of reactive oxygen species generation, the maintenance of ion homeostasis, and the protection of neurovascular units in cultured glial cells. In an animal model, a distinct pattern of protein alterations was detected in glia following hypothermia under ischemic/reperfusion conditions. In particular, hypothermia was found to exert a neuroprotective effect against ischemic brain injury by regulating specific glial signaling pathways, such as, glutamate signaling, cell death, and stress response, and by influencing neural dysfunction, neurogenesis, neural plasticity, cell differentiation, and neurotrophic activity. Furthermore, the proteins that were differentially expressed belonged to various pathways and could mediate diverse phenotypic changes of glia in vitro or in vivo. Therefore, hypothermia-modulated glial proteins and subsequent phenotypic changes may form the basis of the therapeutic effects of hypothermia. PMID:23441897

  18. Dipyrone metabolite 4-MAA induces hypothermia and inhibits PGE2-dependent and -independent fever while 4-AA only blocks PGE2-dependent fever

    PubMed Central

    Malvar, David do C; Aguiar, Fernando A; Vaz, Artur de L L; Assis, Débora C R; de Melo, Miriam C C; Jabor, Valquíria A P; Kalapothakis, Evanguedes; Ferreira, Sérgio H; Clososki, Giuliano C; de Souza, Glória E P

    2014-01-01

    BACKGROUND AND PURPOSE The antipyretic and hypothermic prodrug dipyrone prevents PGE2-dependent and -independent fever induced by LPS from Escherichia coli and Tityus serrulatus venom (Tsv) respectively. We aimed to identify the dipyrone metabolites responsible for the antipyretic and hypothermic effects. EXPERIMENTAL APPROACH Male Wistar rats were treated i.p. with indomethacin (2 mg·kg−1), dipyrone, 4-methylaminoantipyrine (4-MAA), 4-aminoantipyrine (4-AA) (60–360 mg·kg−1), 4-formylaminoantipyrine, 4-acethylaminoantipyrine (120–360 mg·kg−1) or vehicle 30 min before i.p. injection of LPS (50 μg·kg−1), Tsv (150 μg·kg−1) or saline. Rectal temperatures were measured by tele-thermometry and dipyrone metabolite concentrations determined in the plasma, CSF and hypothalamus by LC-MS/MS. PGE2 concentrations were determined in the CSF and hypothalamus by elisa. KEY RESULTS In contrast to LPS, Tsv-induced fever was not followed by increased PGE2 in the CSF or hypothalamus. The antipyretic time-course of 4-MAA and 4-AA on LPS-induced fever overlapped with the period of the highest concentrations of 4-MAA and 4-AA in the hypothalamus, CSF and plasma. These metabolites reduced LPS-induced fever and the PGE2 increase in the plasma, CSF and hypothalamus. Only 4-MAA inhibited Tsv-induced fever. The higher doses of dipyrone and 4-MAA also induced hypothermia. CONCLUSIONS AND IMPLICATIONS The presence of 4-MAA and 4-AA in the CSF and hypothalamus was associated with PGE2 synthesis inhibition and a decrease in LPS-induced fever. 4-MAA was also shown to be an antipyretic metabolite for PGE2-independent fever induced by Tsv suggesting that it is responsible for the additional antipyretic mechanism of dipyrone. Moreover, 4-MAA is the hypothermic metabolite of dipyrone. PMID:24712707

  19. Hypothermia and the trauma patient

    PubMed Central

    Kirkpatrick, Andrew W.; Chun, Rosaleen; Brown, Ross; Simons, Richard K.

    Hypothermia has profound effects on every system in the body, causing an overall slowing of enzymatic reactions and reduced metabolic requirements. Hypothermic, acutely injured patients with multisystem trauma have adverse outcomes when compared with normothermic control patients. Trauma patients are inherently predisposed to hypothermia from a variety of intrinsic and iatrogenic causes. Coagulation and cardiac sequelae are the most pertinent physiological concerns. Hypothermia and coagulopathy often mandate a simplified approach to complex surgical problems. A modification of traditional classification systems of hypothermia, applicable to trauma patients is suggested. There are few controlled investigations, but clinical opinion strongly supports the active prevention of hypothermia in the acutely traumatized patient. Preventive measures are simple and inexpensive, but the active reversal of hypothermia is much more complicated, often invasive and controversial. The ideal method of rewarming is unclear but must be individualized to the patient and is institution specific. An algorithm reflecting newer approaches to traumatic injury and technical advances in equipment and techniques is suggested. Conversely, hypothermia has selected clinical benefits when appropriately used in cases of trauma. Severe hypothermia has allowed remarkable survivals in the course of accidental circulatory arrest. The selective application of mild hypothermia in severe traumatic brain injury is an area with promise. Deliberate circulatory arrest with hypothermic cerebral protection has also been used for seemingly unrepairable injuries and is the focus of ongoing research. PMID:10526517

  20. Prevention of inadvertent perioperative hypothermia.

    PubMed

    Burger, Leona; Fitzpatrick, Jane

    All patients undergoing surgery are at risk of developing hypothermia; up to 70% develop hypothermia perioperatively. Inadvertent hypothermia is associated with complications such as impaired wound healing, increased blood loss, cardiac arrest and increased risk of wound infection. Anaesthesia increases the risk as the normal protective shivering reflex is absent. Ambient temperature also has a major effect on the patient's body temperature. Prevention of hypothermia not only reduces the incidence of complications, but patients also experience a greater level of comfort, and avoid postoperative shivering and the unpleasant sensation of feeling cold. Nurses should be aware of the risks of hypothermia so that preventative interventions can be employed to minimize the risk of hypothermia. Preoperative assessment is essential to enable identification of at-risk patients. Simple precautionary measures initiated by nurses can considerably reduce the amount of heat lost, minimize the risk of associated complications and ultimately improve patients' short- and long-term recovery. Minimizing skin exposure, providing adequate bed linen for the transfer to theatre and educating patients about the importance of keeping warm perioperatively are all extremely important. It is also worth considering using forced-air warmers preoperatively as research suggests that initiating active warming preoperatively may be successful in preventing hypothermia during the perioperative period. PMID:19966730

  1. Peripheral Adenosine A3 Receptor Activation Causes Regulated Hypothermia in Mice That Is Dependent on Central Histamine H1 Receptors.

    PubMed

    Carlin, Jesse Lea; Tosh, Dilip K; Xiao, Cuiying; Piñol, Ramón A; Chen, Zhoumou; Salvemini, Daniela; Gavrilova, Oksana; Jacobson, Kenneth A; Reitman, Marc L

    2016-02-01

    Adenosine can induce hypothermia, as previously demonstrated for adenosine A1 receptor (A1AR) agonists. Here we use the potent, specific A3AR agonists MRS5698, MRS5841, and MRS5980 to show that adenosine also induces hypothermia via the A3AR. The hypothermic effect of A3AR agonists is independent of A1AR activation, as the effect was fully intact in mice lacking A1AR but abolished in mice lacking A3AR. A3AR agonist-induced hypothermia was attenuated by mast cell granule depletion, demonstrating that the A3AR hypothermia is mediated, at least in part, via mast cells. Central agonist dosing had no clear hypothermic effect, whereas peripheral dosing of a non-brain-penetrant agonist caused hypothermia, suggesting that peripheral A3AR-expressing cells drive the hypothermia. Mast cells release histamine, and blocking central histamine H1 (but not H2 or H4) receptors prevented the hypothermia. The hypothermia was preceded by hypometabolism and mice with hypothermia preferred a cooler environmental temperature, demonstrating that the hypothermic state is a coordinated physiologic response with a reduced body temperature set point. Importantly, hypothermia is not required for the analgesic effects of A3AR agonists, which occur with lower agonist doses. These results support a mechanistic model for hypothermia in which A3AR agonists act on peripheral mast cells, causing histamine release, which stimulates central histamine H1 receptors to induce hypothermia. This mechanism suggests that A3AR agonists will probably not be useful for clinical induction of hypothermia. PMID:26606937

  2. Peripheral Adenosine A3 Receptor Activation Causes Regulated Hypothermia in Mice That Is Dependent on Central Histamine H1 Receptors

    PubMed Central

    Carlin, Jesse Lea; Tosh, Dilip K.; Xiao, Cuiying; Piñol, Ramón A.; Chen, Zhoumou; Salvemini, Daniela; Gavrilova, Oksana; Jacobson, Kenneth A.

    2016-01-01

    Adenosine can induce hypothermia, as previously demonstrated for adenosine A1 receptor (A1AR) agonists. Here we use the potent, specific A3AR agonists MRS5698, MRS5841, and MRS5980 to show that adenosine also induces hypothermia via the A3AR. The hypothermic effect of A3AR agonists is independent of A1AR activation, as the effect was fully intact in mice lacking A1AR but abolished in mice lacking A3AR. A3AR agonist–induced hypothermia was attenuated by mast cell granule depletion, demonstrating that the A3AR hypothermia is mediated, at least in part, via mast cells. Central agonist dosing had no clear hypothermic effect, whereas peripheral dosing of a non–brain-penetrant agonist caused hypothermia, suggesting that peripheral A3AR-expressing cells drive the hypothermia. Mast cells release histamine, and blocking central histamine H1 (but not H2 or H4) receptors prevented the hypothermia. The hypothermia was preceded by hypometabolism and mice with hypothermia preferred a cooler environmental temperature, demonstrating that the hypothermic state is a coordinated physiologic response with a reduced body temperature set point. Importantly, hypothermia is not required for the analgesic effects of A3AR agonists, which occur with lower agonist doses. These results support a mechanistic model for hypothermia in which A3AR agonists act on peripheral mast cells, causing histamine release, which stimulates central histamine H1 receptors to induce hypothermia. This mechanism suggests that A3AR agonists will probably not be useful for clinical induction of hypothermia. PMID:26606937

  3. 24-hour control of body temperature in the rat: II. Diisopropyl fluorophosphate-induced hypothermia and hyperthermia.

    PubMed

    Gordon, C J

    1994-11-01

    Diisopropyl fluorophosphate (DFP) and other anticholinesterase (antiChE) agents have been found to induce marked hypothermic responses in laboratory rodents. To characterize the effects of DFP on autonomic and behavioral thermoregulation, rats of the Long-Evans strain were injected with DFP while housed in a temperature gradient. The gradient allowed for the measurement of selected ambient temperature (Ta) and motor activity (MA) over a 6- to 7-day period. Core temperature (Tc) and heart rate (HR) were also monitored simultaneously using radiotelemetry. Injection of the peanut oil vehicle led to transient elevations in Tc, HR, and MA, but no change in selected Ta. The next day animals were injected with 0.25, 1.0, or 1.5 mg/kg DFP. DFP (1.0 AND 1.5 mg/kg) led to a marked reduction in Tc. The decrease in Tc was accompanied by reductions in HR, MA, and selected Ta. During the first night after DFP, selected Ta remained elevated as Tc recovered to its preinjection level. The second 24-h period after 1.0 and 1.5 mg/kg DFP was associated with a significant elevation in the daytime Tc. In conclusion, with the option of using behavioral thermoregulatory responses, the hypothermic effects of acute DFP treatment are mediated by a selection for cooler TaS. An elevation in Tc during recovery from acute DFP corroborates the many incidents of fever in humans exposed to anti-ChE agents. PMID:7862732

  4. Environmental hypothermia in porcine polytrauma and hemorrhagic shock is safe.

    PubMed

    Iyegha, Uroghupatei P; Greenberg, Joseph J; Mulier, Kristine E; Chipman, Jeffrey; George, Mark; Beilman, Greg J

    2012-10-01

    We have previously demonstrated survival benefit to induced hypothermia in a porcine model of controlled hemorrhagic shock simulating an associated delay to definitive care. In the current study, we wished to evaluate the effects of environmental hypothermia in a porcine model of hemorrhagic shock with the addition of polytrauma. Sixteen pigs were randomized to normothermic (39°C, n = 7) or hypothermic (34°C, n = 9) groups. The model included instrumentation, chest injury (captive bolt device), hemorrhage to systolic blood pressure (SBP) of ∼50 mmHg, and crush liver injury. Animals received limited fluid resuscitation for a 1-h period with goal SBP of greater than 80 mmHg and ice packs or warming blankets to achieve goal temperatures, followed by full resuscitation with goal SBP of greater than 90 mmHg, adequate urine output, and hemoglobin by protocol for 20 h. Survivors were observed for an additional 24 h with end points including mortality, markers of organ injury, and neurologic function. There were no differences in survival between the groups (mortality = 1/9, hypothermia group vs. 2/7, normothermia group, P = 0.39). Markers of organ injury were elevated in the hypothermia group at 24 h after injury but were identical between groups at the end of the experimental protocol (48 h after injury). There were no noted differences in neurologic function between the two groups. Environmental hypothermia in a model of polytrauma and hemorrhagic shock was not associated with worse outcomes. PMID:22777118

  5. Functional laser speckle imaging of cerebral blood flow under hypothermia

    NASA Astrophysics Data System (ADS)

    Li, Minheng; Miao, Peng; Zhu, Yisheng; Tong, Shanbao

    2011-08-01

    Hypothermia can unintentionally occur in daily life, e.g., in cardiovascular surgery or applied as therapeutics in the neurosciences critical care unit. So far, the temperature-induced spatiotemporal responses of the neural function have not been fully understood. In this study, we investigated the functional change in cerebral blood flow (CBF), accompanied with neuronal activation, by laser speckle imaging (LSI) during hypothermia. Laser speckle images from Sprague-Dawley rats (n = 8, male) were acquired under normothermia (37°C) and moderate hypothermia (32°C). For each animal, 10 trials of electrical hindpaw stimulation were delivered under both temperatures. Using registered laser speckle contrast analysis and temporal clustering analysis (TCA), we found a delayed response peak and a prolonged response window under hypothermia. Hypothermia also decreased the activation area and the amplitude of the peak CBF. The combination of LSI and TCA is a high-resolution functional imaging method to investigate the spatiotemporal neurovascular coupling in both normal and pathological brain functions.

  6. Pharmacological hypothermia: a potential for future stroke therapy?

    PubMed

    Liu, Kaiyin; Khan, Hajra; Geng, Xiaokun; Zhang, Jun; Ding, Yuchuan

    2016-06-01

    Mild physical hypothermia after stroke has been associated with positive outcomes. Despite the well-studied beneficial effects of hypothermia in the treatment of stroke, lack of precise temperature control, intolerance for the patient, and immunosuppression are some of the reasons which limit its clinical translation. Pharmacologically induced hypothermia has been explored as a possible treatment option following stroke in animal models. Currently, there are eight classes of pharmacological agents/agonists with hypothermic effects affecting a multitude of systems including cannabinoid, opioid, transient receptor potential vanilloid 1 (TRPV1), neurotensin, thyroxine derivatives, dopamine, gas, and adenosine derivatives. Interestingly, drugs in the TRPV1, neurotensin, and thyroxine families have been shown to have effects in thermoregulatory control in decreasing the compensatory hypothermic response during cooling. This review will briefly present drugs in the eight classes by summarizing their proposed mechanisms of action as well as side effects. Reported thermoregulatory effects of the drugs will also be presented. This review offers the opinion that these agents may be useful in combination therapies with physical hypothermia to achieve faster and more stable temperature control in hypothermia. PMID:27320243

  7. Halting Hypothermia: Cold Can Be Dangerous

    MedlinePlus

    ... who spends much time outdoors in very cold weather can get hypothermia. But hypothermia can happen anywhere— ... just outside and not just in bitter winter weather. It can strike when temperatures are cool—for ...

  8. Inadvertent Perianesthetic Hypothermia in Small Animal Patients.

    PubMed

    Clark-Price, Stuart

    2015-09-01

    Inadvertent perianesthetic hypothermia is one of the most common complications in anesthesia of dogs and cats. Hypothermia during anesthesia can lead to altered pharmacokinetics of anesthetic and analgesic drugs, dysfunction of organ systems, increased patient susceptibility to infection, reduced wound healing, altered coagulation, hypotension, and delayed recovery. An understanding of the pathophysiology, complications, and techniques to minimize hypothermia during anesthesia can help veterinarians optimize care of patients. This article provides an overview of inadvertent perianesthetic hypothermia. PMID:26014270

  9. Hypothermia inhibits the propagation of acute ischemic injury by inhibiting HMGB1.

    PubMed

    Lee, Jung Ho; Yoon, Eun Jang; Seo, Jeho; Kavoussi, Adriana; Chung, Yong Eun; Chung, Sung Phil; Park, Incheol; Kim, Chul Hoon; You, Je Sung

    2016-01-01

    Acute ischemic stroke causes significant chronic disability worldwide. We designed this study to clarify the mechanism by which hypothermia helps alleviate acute ischemic stroke. In a middle cerebral artery occlusion model (4 h ischemia without reperfusion), hypothermia effectively reduces mean infarct volume. Hypothermia also prevents neurons in the infarct area from releasing high mobility group box 1 (HMGB1), the most well-studied damage-associated molecular pattern protein. By preventing its release, hypothermia also prevents the typical middle cerebral artery occlusion-induced increase in serum HMGB1. We also found that both glycyrrhizin-mediated inhibition of HMGB1 and intracerebroventricular neutralizing antibody treatments before middle cerebral artery occlusion onset diminish infarct volume. This suggests a clear neuroprotective effect of HMGB1 inhibition by hypothermia in the brain. We next used real-time polymerase chain reaction to measure the levels of pro-inflammatory cytokines in peri-infarct regions. Although middle cerebral artery occlusion increases the expression of interleukin-1β and tissue necrosis factor-α, this elevation is suppressed by both hypothermia and glycyrrhizin treatment. We show that hypothermia reduces the production of inflammatory cytokines and helps salvage peri-infarct regions from the propagation of ischemic injury via HMGB1 blockade. In addition to suggesting a potential mechanism for hypothermia's therapeutic effects, our results suggest HMGB1 modulation may lengthen the therapeutic window for stroke treatments. PMID:27544687

  10. Therapeutic hypothermia in neonatal asphyxia

    PubMed Central

    Cornette, L.

    2012-01-01

    Hypoxic ischemic encephalopathy is a serious condition affecting newborn infants which can result in death and disability. There is now strong clinical evidence that moderate post-asphyxial total body cooling or hypothermia in full term neonates results in long-term neuroprotection, allowing us to proclaim this innovative therapy as “standard of care.” The treatment is a time-critical emergency and should be started within 6 hours after the insult. Such requires optimal collaboration among local hospitals, transport teams and the closest neonatal intensive care unit. The technique is only safe when applied according to published clinical trial protocols, and with admission of these patients to a neonatal intensive care unit. Future studies should be aimed at optimizing the onset, duration, and depth of hypothermia. Combination of hypothermia and drugs may further improve neuroprotection in asphyxiated full term neonates. PMID:24753900

  11. Glibenclamide enhances the effects of delayed hypothermia after experimental stroke in rats.

    PubMed

    Wu, Zhou; Zhu, Shu-Zhen; Hu, Ya-Fang; Gu, Yong; Wang, Sheng-Nan; Lin, Zhen-Zhou; Xie, Zuo-Shan; Pan, Su-Yue

    2016-07-15

    In order to evaluate whether glibenclamide can extend the therapeutic window during which induced hypothermia can protect against stroke, we subjected adult male Sprague-Dawley rats to middle cerebral artery occlusion (MCAO). We first verified the protective effects of hypothermia induced at 0, 2, 4 or 6h after MCAO onset, and then we assessed the effects of the combination of glibenclamide and hypothermia at 6, 8 or 10h after MCAO onset. At 24h after MCAO, we assessed brain edema, infarct volume, modified neurological severity score, Evans Blue leakage and expression of Sulfonylurea receptor 1 (SUR1) protein and pro-inflammatory factors. No protective effects were observed when hypothermia was induced too long after MCAO. At 6h after MCAO onset, hypothermia alone failed to decrease cerebral edema and infarct volume, but the combination of glibenclamide and hypothermia decreased both. The combination also improved neurological outcome, ameliorated blood-brain barrier damage and decreased levels of COX-2, TNF-α and IL-1β. These results suggest that glibenclamide enhances and extends the therapeutic effects of delayed hypothermia against ischemia stroke, potentially by ameliorating blood-brain barrier damage and declining levels of pro-inflammatory factors. PMID:27134036

  12. Adrenocortical response in rats subjected to a stress of restraint by immobilization whether accompanied by hypothermia or not

    NASA Technical Reports Server (NTRS)

    Buchel, L.; Prioux-Guyonneau, M.; Libian, L.

    1980-01-01

    The restraint associated with hypothermia which increases the adrenal activity in rats was investigated. In rats with nomothermia or light hypothermia, the plasma and adrenal corticosterone levels increase at least threefold whatever the duration of restraint. Their return to normal values depends on the duration of the restraint. Exposure to cold produces in free rats a light hypothermia with an increase of the plasma and adrenal corticosterone levels, and in restraint animals an important hypothermia which does not potentiate the stimulation of adrenocortical activity induced by the restraint alone.

  13. HYPOTHERMIA AND CHLOROPENT ANESTHESIA DIFFERENTIALLY AFFECT THE FLASH EVOKED POTENTIALS OF HOODED RATS

    EPA Science Inventory

    Anesthetics and body temperature alterations are both known to alter parameters of sensory-evoked responses. However few studies have quantitatively assessed the contributions of hypothermia to anesthetic-induced changes. Two experiments were performed. In the first, chronically ...

  14. S 14297, a novel selective ligand at cloned human dopamine D3 receptors, blocks 7-OH-DPAT-induced hypothermia in rats.

    PubMed

    Millan, M J; Audinot, V; Rivet, J M; Gobert, A; Vian, J; Prost, J F; Spedding, M; Peglion, J L

    1994-08-01

    The selective dopamine D3 receptor agonist, 7-OH-DPAT ((+)-7-hydroxy-2-(di-n-propylamino)tetralin) and the novel naphthofurane, S 14297 ((+)-[7-(N,N-dipropylamino)-5,6,7,8-tetrahydro- naphtho(2,3b)dihydro,2,3-furane]), bound with high affinity and selectivity to recombinant, human dopamine D3 versus D2 receptors stably transfected into Chinese hamster ovary cells: Ki values = 2 versus 103 nM for 7-OH-DPAT and 13 versus 297 nM for S 14297. In contrast, the putative dopamine D3 receptor antagonist, AJ 76 (cis-(+)-5-methoxy-1-methyl-2-(n- propylamino)tetralin), displayed low affinity and selectivity for dopamine D3 versus D2 sites (70 versus 154 nM). 7-OH-DPAT (0.01-0.16 mg/kg s.c.) provoked hypothermia in rats, an action abolished by S 14297 (0.04-0.63 mg/kg s.c.) and, less potently, by AJ 76 (0.16-2.5 mg/kg s.c.). S 14297 (20.0 mg/kg s.c.) did not modify prolactin secretion. These data suggest that dopamine D3 receptors mediate hypothermia in the rat and that S 14297 acts as a selective antagonist at these sites. PMID:7988633

  15. The Cold Blooded Killer: Hypothermia.

    ERIC Educational Resources Information Center

    Keller, Rosanne

    Part of a series of home literacy readers with conversational text and sketches, this booklet depicts the subarctic Alaskan environment where cold makes extreme demands on body metabolism. Body temperature must be maintained above 80F (26.7C). A condition of too little body-heat is termed hypo- ('deficit') thermia ('heat'). Hypothermia is the…

  16. Detrimental effect of hypothermia during acute normovolaemic haemodilution in anaesthetized cats

    NASA Astrophysics Data System (ADS)

    Talwar, A.; Fahim, Mohammad

    Haemodynamic responses to hypothermia were studied at normal haematocrit and following the induction of acute normovolaemic haemodilution. Experiments were performed on 20 cats anaesthetized with a mixture of chloralose and urethane in two groups. In one group (n=10) the effects of hypothermia on various haemodynamic variables were studied at normal haematocrit (41.0+/-1.7%) and in the second group of cats (n=10) the effects of hypothermia on various haemodynamic variables were studied after the induction of acute normovolaemic haemodilution (14.0+/-1.0%). The haemodynamic variables left ventricular pressure, left ventricular contractility, arterial blood pressure, heart rate and right atrial pressure were recorded on a polygraph. Cardiac output was measured using a cardiac output computer. In both groups hypothermia was induced by surface cooling with the help of ice. Cardiovascular variables were recorded at each 1° C fall in body temperature. Hypothermia produced a significant (P<0.05) drop in heart rate, cardiac output, arterial blood pressure and left ventricular contractility in both groups. However, the percentage decrease in these variables in response to hypothermia was significantly (P<0.05) higher in cats with low haematocrit than in those with normal haematocrit. The severity of hypothermia - induced cardiovascular effects is evident from the drastic decrease in heart rate, cardiac output, arterial blood pressure and myocardial contractility in cats with low haematocrit, indicating a higher risk of circulatory failure under anaemic conditions at low temperatures.

  17. Pharmacologic options for reducing the shivering response to therapeutic hypothermia.

    PubMed

    Weant, Kyle A; Martin, Julia E; Humphries, Roger L; Cook, Aaron M

    2010-08-01

    Recent literature has demonstrated significant improvements in neurologic outcomes in patients who have received induced hypothermia in the setting of out-of-hospital cardiac arrest. Through multiple metabolic mechanisms, the induction of hypothermia slows the progression and devastation of transient cerebral hypoxia. Despite these benefits, the desired reduction in core temperature is often a challenging venture as the body attempts to maintain homeostasis through the induction of thermoregulatory processes aimed at elevating body temperature. Shivering is an involuntary muscular activity that enhances heat production in an attempt to restore homeostasis. For successful induction and maintenance of induced hypothermia, shivering, as well as other thermoregulatory responses, must be overcome. Several pharmacologic options are available, either used alone or in combination, that safely and effectively prevent or treat shivering after the induction of hypothermia. We conducted a PubMed search (1966-March 2009) to identify all human investigations published in English that discussed pharmacologic mechanisms for the control of shivering. Among these options, clonidine, dexmedetomidine, and meperidine have demonstrated the greatest and most clinically relevant impact on depression of the shivering threshold. More research in this area is needed, however, and the role of the clinical pharmacist in the development and implementation of this therapy needs to be defined. PMID:20653360

  18. Out-of-hospital therapeutic hypothermia in cardiac arrest victims

    PubMed Central

    Behringer, Wilhelm; Arrich, Jasmin; Holzer, Michael; Sterz, Fritz

    2009-01-01

    Despite many years of research, outcome after cardiac arrest is dismal. Since 2005, the European Resuscitation Council recommends in its guidelines the use of mild therapeutic hypothermia (32-34°) for 12 to 24 hours in patients successfully resuscitated from cardiac arrest. The benefit of resuscitative mild hypothermia (induced after resuscitation) is well established, while the benefit of preservative mild to moderate hypothermia (induced during cardiac arrest) needs further investigation before recommending it for clinical routine. Animal data and limited human data suggest that early and fast cooling might be essential for the beneficial effect of resuscitative mild hypothermia. Out-of-hospital cooling has been shown to be feasible and safe by means of intravenous infusion with cold fluids or non-invasively with cooling pads. A combination of these cooling methods might further improve cooling efficacy. If out-of-hospital cooling will further improve functional outcome as compared with in-hospital cooling needs to be determined in a prospective, randomised, sufficiently powered clinical trial. PMID:19821966

  19. Myocardial protection with mild hypothermia.

    PubMed

    Tissier, Renaud; Ghaleh, Bijan; Cohen, Michael V; Downey, James M; Berdeaux, Alain

    2012-05-01

    Mild hypothermia, 32-35° C, is very potent at reducing myocardial infarct size in rabbits, dogs, sheep, pigs, and rats. The benefit is directly related to reduction in normothermic ischaemic time, supporting the relevance of early and rapid cooling. The cardioprotective effect of mild hypothermia is not limited to its recognized reduction of infarct size, but also results in conservation of post-ischaemic contractile function, prevention of no-reflow or microvascular obstruction, and ultimately attenuation of left ventricular remodelling. The mechanism of the anti-infarct effect does not appear to be related to diminished energy utilization and metabolic preservation, but rather to survival signalling that involves either the extracellular signal-regulated kinases and/or the Akt/phosphoinositide 3-kinase/mammalian target of rapamycin pathways. Initial clinical trials of hypothermia in patients with ST-segment elevation myocardial infarction were disappointing, probably because cooling was too slow to shorten normothermic ischaemic time appreciably. New approaches to more rapid cooling have recently been described and may soon be available for clinical use. Alternatively, it may be possible to pharmacologically mimic the protection provided by cooling soon after the onset of ischaemia with an activator of mild hypothermia signalling, e.g. extracellular signal-regulated kinase activator, that could be given by emergency medical personnel. Finally, the protection afforded by cooling can be added to that of pre- and post-conditioning because their mechanisms differ. Thus, myocardial salvage might be greatly increased by rapidly cooling patients as soon as possible and then giving a pharmacological post-conditioning agent immediately prior to reperfusion. PMID:22131353

  20. The big chill: accidental hypothermia.

    PubMed

    Davis, Robert Allan

    2012-01-01

    A potential cause of such emergent issues as cardiac arrhythmias, hypotension, and fluid and electrolyte shifts, accidental hypothermia can be deadly, is common among trauma patients, and is often difficult to recognize. The author discusses predisposing conditions, the classic presentation, and the effects on normal thermoregulatory processes; explains how to conduct a systems assessment of the hypothermic patient; and describes crucial management strategies. PMID:22186703

  1. [Hypothermia--mechanism of action and pathophysiological changes in the human body].

    PubMed

    Sosnowski, Przemysław; Mikrut, Kinga; Krauss, Hanna

    2015-01-01

    This review focuses on the physiological responses and pathophysiological changes induced by hypothermia. Normal body function depends on its ability to maintain thermal homeostasis. The human body can be divided arbitrarily into two thermal compartments: a core compartment (trunk and head), with precisely regulated temperature around 37°C, and a peripheral compartment (skin and extremities) with less strictly controlled temperature, and lower than the core temperature. Thermoregulatory processes occur in three phases: afferent thermal sensing, central regulation, mainly by the preoptic area of the anterior hypothalamus, and efferent response. Exposure to cold induces thermoregulatory responses including cutaneous vasoconstriction, shivering and non-shivering thermogenesis, and behavioral changes. Alterations of body temperature associated with impaired thermoregulation, decreased heat production or increased heat loss can lead to hypothermia. Hypothermia is defined as a core body temperature below 35ºC, and may be classified according to the origin as accidental (e.g. caused by exposure to a cold environment, drugs, or illness) or intentional (i.e. therapeutic), or by the degree of hypothermia as mild, moderate or severe. Classification by temperature is not universal. Lowering of body temperature disrupts the physiological processes at the molecular, cellular and system level, but hypothermia induced prior to cardiosurgical or neurosurgical procedures, by the decrease in tissue oxygen demand, can reduce the risk of cerebral or cardiac ischemic damage. Therapeutic hypothermia has been recommended as a clinical procedure in situations characterized by ischemia, such as cardiac arrest, stroke and brain injuries. PMID:25614675

  2. Activation of mitochondrial STAT-3 and reduced mitochondria damage during hypothermia treatment for post-cardiac arrest myocardial dysfunction.

    PubMed

    Huang, Chien-Hua; Tsai, Min-Shan; Chiang, Chih-Yen; Su, Yu-Jen; Wang, Tzung-Dau; Chang, Wei-Tien; Chen, Huei-Wen; Chen, Wen-Jone

    2015-11-01

    While therapeutic hypothermia improves the outcomes of individuals in cardiac arrest, the hemodynamic responses and mechanisms which underlie hypothermia-induced cardioprotection are not fully understood. Therefore, we investigated the mechanism by which induced hypothermia preserves cardiac function and protects against mitochondrial damage following cardiac arrest. Cardiac arrest was induced in adult male Wistar rats by asphyxiation for 8.5 min. Following resuscitation, the animals were randomly assigned to a hypothermia (32 °C) or normothermia (37 °C) group. Monitoring results showed that cardiac output at the fourth hour after resuscitation was significantly better in rats treated with hypothermia when compared to rats treated with normothermia (P < 0.01). Examinations by transmission electron microscopy showed that mitochondria in the left ventricle of rats in the hypothermia group were significantly less swollen compared to such mitochondria in the normothermia group (P < 0.001). Additionally, opening of mitochondrial permeability transition pores occurred less frequently in the hypothermic group. While complex I/III activity in the electron transport reaction was damaged after cardiac arrest and resuscitation, the degree of injury was ameliorated by hypothermia treatment (P < 0.05). The amount of STAT-3 phosphorylated at tyrosine 705 and its expression in mitochondria were significantly higher under hypothermia treatment compared to normothermia treatment. In vitro studies showed that inhibition STAT-3 activation abolished the ability of hypothermia to protect H9C2 cardiomyocytes against injury produced by simulated ischemia and reperfusion. Therapeutic hypothermia treatment can ameliorate cardiac dysfunction and help preserve both mitochondrial integrity and electron transport activity. PMID:26471891

  3. The Lonely Mouse – Single Housing Affects Serotonergic Signaling Integrity Measured by 8-OH-DPAT-Induced Hypothermia in Male Mice

    PubMed Central

    Kalliokoski, Otto; Teilmann, A. Charlotte; Jacobsen, Kirsten R.; Abelson, Klas S. P.; Hau, Jann

    2014-01-01

    Male BALB/c mice single-housed for a period of three weeks were found to respond with a more marked hypothermia to a challenge with a selective serotonergic agonist (8-OH-DPAT) than their group-housed counterparts. This effect of single housing was verified by screening a genetically heterogeneous population of male mice on a C57BL/6 background from a breeding colony. Enhanced activity of the implicated receptor (5-HT1A) leading to an amplified hypothermic effect is strongly associated with depressive states. We therefore suggest that the 8-OH-DPAT challenge can be used to demonstrate a negative emotional state brought on by e.g. long-term single housing in male laboratory mice. The study emphasizes the importance of social housing, and demonstrates that male mice deprived of social contact respond with altered serotonergic signaling activity. Male mice not only choose social contact when given the option, as has previously been shown, but will also, when it is deprived, be negatively affected by its absence. We propose that the 8-OH-DPAT challenge constitutes a simple, but powerful, tool capable of manifesting the effect of social deprivation in laboratory mice. It potentially allows not only for an unbiased, biochemical evaluation of psychological stressors, but may also allow for determining whether the effect of these can be counteracted. PMID:25436462

  4. Food restriction alters N'-propyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine dihydrochloride (pramipexole)-induced yawning, hypothermia, and locomotor activity in rats: evidence for sensitization of dopamine D2 receptor-mediated effects.

    PubMed

    Collins, Gregory T; Calinski, Diane M; Newman, Amy Hauck; Grundt, Peter; Woods, James H

    2008-05-01

    Food restriction enhances sensitivity to the reinforcing effects of a variety of drugs of abuse including opiates, nicotine, and psychostimulants. Food restriction has also been shown to alter a variety of behavioral and pharmacological responses to dopaminergic agonists, including an increased sensitivity to the locomotor stimulatory effects of direct- and indirect-dopamine agonists, elevated extracellular dopamine levels in responses to psychostimulants, as well as suppression of agonist-induced yawning. Behavioral and molecular studies suggest that augmented dopaminergic responses observed in food-restricted animals result from a sensitization of the dopamine D2 receptor; however, little is known about how food restriction affects dopamine D3 receptor function. The current studies were aimed at better defining the effects of food restriction on D2 and D3 receptor function by assessing the capacity of N'-propyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine dihydrochloride (pramipexole) to induce yawning, penile erection (PE), hypothermia, and locomotor activity in free-fed and food-restricted rats. Food restriction resulted in a suppression of pramipexole-induced yawning, a sensitized hypothermic response, and an enhanced locomotor response to pramipexole, effects that are suggestive of an enhanced D2 receptor activity; no effect on pramipexole-induced PE was observed. Antagonist studies further supported a food restriction-induced enhancement of the D2 receptor activity because the D2 antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1H-indole (L741,626) recovered pramipexole-induced yawning to free-fed levels, whereas yawning and PE were suppressed following pretreatment with the D3 antagonist N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide hydrochloride (PG01037). The results of the current studies suggest that food restriction sensitized rats to the D2-mediated effects of pramipexole while having no effect

  5. Hypothermia as a clinical neuroprotectant.

    PubMed

    Sherman, Andrew L; Wang, Michael Y

    2014-08-01

    Applying therapeutic hypothermia (TH) for the purposes of neuroprotection, originally termed "hibernation," started nearly 100 years ago. Because TH cooling systems have improved to the point where it is practical and safe for general application, interest in providing such treatment in conditions such as spinal cord injury, traumatic brain injury, stroke, and cardiac arrest has increased. This article reviews the mechanisms by which TH mitigates secondary neurologic injury, the clinical scenarios where TH is being applied, and reviews selected published studies using TH for central nervous system neuroprotection. PMID:25064786

  6. Moderate Hypothermia Significantly Decreases Hippocampal Cell Death Involving Autophagy Pathway after Moderate Traumatic Brain Injury

    PubMed Central

    Jin, Yichao; Lin, Yingying; Feng, Jun-feng; Jia, Feng; Gao, Guo-yi

    2015-01-01

    Abstract Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI) followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were randomly divided into four groups: sham injury with normothermia group (37°C); sham injury with hypothermia group (32°C); TBI with normothermia group (TNG; 37°C); and TBI with hypothermia group (THG; 32°C). Injury was induced by a fluid percussion TBI device. Moderate hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 h. All rats were killed at 24 h after fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; terminal deoxynucleoitidyl transferase-mediated nick end labeling staining was used to determine cell death in ipsilateral hippocampus. Immunohistochemistry and western blotting of microtubule-associated protein light chain 3 (LC3), Beclin-1, as well as transmission electron microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell death index was 27.90±2.36% in TNG and 14.90±1.52% in THG. Expression level of LC3 and Beclin-1 were significantly increased after TBI and were further up-regulated after post-TBI hypothermia. Further, ultrastructural observations showed that there was a marked increase of autophagosomes and autolysosomes in ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that moderate hypothermia significantly attenuated cell death and increased autophagy in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy pathway may participate in the neuroprotective effect of post-TBI hypothermia. PMID:25942484

  7. Therapeutic hypothermia for acute ischemic stroke.

    PubMed

    Froehler, Michael T; Ovbiagele, Bruce

    2010-04-01

    Intravenous recombinant tissue plasminogen activator remains the only US FDA-approved treatment for acute ischemic stroke. However, the very limited time window for its administration restricts its usefulness. Furthermore, it is becoming increasingly clear that, given the numerous pathways via which cerebral ischemia causes cell death, the capacity to inhibit multiple mechanisms simultaneously may provide additive or synergistic beneficial clinical effects for stroke patients. Although no clinical trials have yet investigated the efficacy of therapeutic hypothermia in focal cerebral ischemia, its pleiotropic neuroprotective actions, positive results in preclinical studies, as well as proven enhancement of neurologic outcomes in survivors of cardiac arrest and newborns with hypoxic-ischemic encephalopathy, make this neuroprotective strategy highly promising. This review presents an overview of the potential role of hypothermia in the treatment of acute ischemic stroke and discusses ischemic cell death pathophysiology, neuroprotective mechanisms of hypothermia, methodologies employed for the induction of hypothermia, results from animal models of cerebral ischemia, and finally, currently available clinical trial data. Two valuable lessons learned thus far are that first, rapid induction of hypothermia is key and is best accomplished with a combination of ice-cold saline infusion and the use of endovascular cooling devices, and second, that shivering can be overcome with aggressive anti-shivering protocols including meperidine, buspirone and surface warming. We await the results of clinical trials to determine the utility of therapeutic hypothermia in acute ischemic stroke. If proven efficacious, hypothermia would be a welcome complement to established reperfusion therapies for ischemic stroke patients. PMID:20397832

  8. Protective Mechanisms of Hypothermia in Liver Surgery and Transplantation

    PubMed Central

    Olthof, Pim B; Reiniers, Megan J; Dirkes, Marcel C; van Gulik, Thomas M; Heger, Michal; van Golen, Rowan F

    2015-01-01

    Hepatic ischemia/reperfusion (I/R) injury is a side effect of major liver surgery that often cannot be avoided. Prolonged periods of ischemia put a metabolic strain on hepatocytes and limit the tolerable ischemia and preservation times during liver resection and transplantation, respectively. In both surgical settings, temporarily lowering the metabolic demand of the organ by reducing organ temperature effectively counteracts the negative consequences of an ischemic insult. Despite its routine use, the application of liver cooling is predicated on an incomplete understanding of the underlying protective mechanisms, which has limited a uniform and widespread implementation of liver-cooling techniques. This review therefore addresses how hypothermia-induced hypometabolism modulates hepatocyte metabolism during ischemia and thereby reduces hepatic I/R injury. The mechanisms underlying hypothermia-mediated reduction in energy expenditure during ischemia and the attenuation of mitochondrial production of reactive oxygen species during early reperfusion are described. It is further addressed how hypothermia suppresses the sterile hepatic I/R immune response and preserves the metabolic functionality of hepatocytes. Lastly, a summary of the clinical status quo of the use of liver cooling for liver resection and transplantation is provided. PMID:26552060

  9. Hypothermia/rewarming disrupts excitation-contraction coupling in cardiomyocytes.

    PubMed

    Schaible, Niccole; Han, Young Soo; Hoang, Thuy; Arteaga, Grace; Tveita, Torkjel; Sieck, Gary

    2016-06-01

    Hypothermia/rewarming (H/R) is poorly tolerated by the myocardium; however, the underlying intracellular basis of H/R-induced cardiac dysfunction remains elusive. We hypothesized that in cardiomyocytes, H/R disrupts excitation-contraction coupling by reducing myofilament Ca(2+) sensitivity due to an increase in cardiac troponin I (cTnI) phosphorylation. To test this hypothesis, isolated rat cardiomyocytes (13-15 cells from 6 rats per group) were electrically stimulated to evoke both cytosolic Ca(2+) ([Ca(2+)]cyto) and contractile (sarcomere shortening) responses that were simultaneously measured using an IonOptix system. Cardiomyocytes were divided into two groups: 1) those exposed to hypothermia (15°C for 2 h) followed by rewarming (35°C; H/R); or 2) time-matched normothermic (35°C) controls (CTL). Contractile dysfunction after H/R was indicated by reduced velocity and extent of sarcomere length (SL) shortening compared with time-matched controls. Throughout hypothermia, basal [Ca(2+)]cyto increased and the duration of evoked [Ca(2+)]cyto transients was prolonged. Phase-loop plots of [Ca(2+)]cyto vs. contraction were shifted rightward in cardiomyocytes during hypothermia compared with CTL, indicating a decrease in Ca(2+) sensitivity. Using Western blot, we found that H/R increases cTnI phosphorylation. These results support our overall hypothesis and suggest that H/R disrupts excitation-contraction coupling of cardiomyocytes due to increased cTnI phosphorylation and reduced Ca(2+) sensitivity. PMID:26993227

  10. MicroRNA-155 potentiates the inflammatory response in hypothermia by suppressing IL-10 production.

    PubMed

    Billeter, Adrian T; Hellmann, Jason; Roberts, Henry; Druen, Devin; Gardner, Sarah A; Sarojini, Harshini; Galandiuk, Susan; Chien, Sufan; Bhatnagar, Aruni; Spite, Matthew; Polk, Hiram C

    2014-12-01

    Therapeutic hypothermia is commonly used to improve neurological outcomes in patients after cardiac arrest. However, therapeutic hypothermia increases sepsis risk and unintentional hypothermia in surgical patients increases infectious complications. Nonetheless, the molecular mechanisms by which hypothermia dysregulates innate immunity are incompletely understood. We found that exposure of human monocytes to cold (32°C) potentiated LPS-induced production of TNF and IL-6, while blunting IL-10 production. This dysregulation was associated with increased expression of microRNA-155 (miR-155), which potentiates Toll-like receptor (TLR) signaling by negatively regulating Ship1 and Socs1. Indeed, Ship1 and Socs1 were suppressed at 32°C and miR-155 antagomirs increased Ship1 and Socs1 and reversed the alterations in cytokine production in cold-exposed monocytes. In contrast, miR-155 mimics phenocopied the effects of cold exposure, reducing Ship1 and Socs1 and altering TNF and IL-10 production. In a murine model of LPS-induced peritonitis, cold exposure potentiated hypothermia and decreased survival (10 vs. 50%; P < 0.05), effects that were associated with increased miR-155, suppression of Ship1 and Socs1, and alterations in TNF and IL-10. Importantly, miR-155-deficiency reduced hypothermia and improved survival (78 vs. 32%, P < 0.05), which was associated with increased Ship1, Socs1, and IL-10. These results establish a causal role of miR-155 in the dysregulation of the inflammatory response to hypothermia. PMID:25231976

  11. Hypothermia

    MedlinePlus

    ... not possible, get the person out of the wind and use a blanket to provide insulation from ... protect your body. These include: Mittens (not gloves) Wind-proof, water-resistant, many-layered clothing Two pairs ...

  12. [Therapeutic hypothermia after cardiac arrest. A cold intravenous fluid, a cooling helmet and a cooling blanket efficiently reduce body temperature].

    PubMed

    Friberg, Hans; Nielsen, Niklas; Karlsson, Torbjörn; Cronberg, Tobias; Widner, Håkan; Englund, Elisabet; Ersson, Anders

    2004-07-22

    Two controlled randomized trials have shown that mild systemic hypothermia after cardiac arrest is beneficial for neurological outcome and one of the studies shows an improved survival rate. A pilot study was performed to evaluate a model of induced hypothermia after cardiac arrest, using cold intravenous fluids and surface cooling with a cold helmet and a coldwater blanket (Thermowrap). The main purpose was to evaluate our cooling method regarding efficacy, safety and usability. Five unconscious patients after cardiac arrest were treated with induced hypothermia of whom three survived with good recovery to six-month follow up. Two patients died in the ICU without regaining consciousness. There were no adverse events during treatment. We conclude that our method is reasonably fast compared to other published methods, it is easy to perform and it offers a good temperature control during cooling and rewarming. Routines for evaluating prognosis and neurological outcome after cardiac arrest and hypothermia treatment need to be revised. PMID:15314936

  13. [Implementation of therapeutic hypothermia into clinical practice].

    PubMed

    Himmel, Friederike; Desch, Steffen; Wolfrum, Sebastian

    2015-08-01

    Implementation of mild therapeutic hypothermia after cardiac arrest into clinical practice is a continuing process. Although ILCOR recommendation was given in 2003, only 24% of the German hospitals reported the use of hypothermia in this setting in 2005. Growing evidence and most importantly the implementation of hypothermia into the guidelines led to a significant increase of acceptance of this therapeutic option leading to a user rate of 69% in 2009. Encouraged by the new guidelines from 2010 86% of German hospitals finally reported to use hypothermia after cardiac arrest routinely in 2012, a decade after publication of the mile stone studies. The phenomenon of a delayed implementation of hypothermia into clinical practice can be seen throughout the world as many surveys from different countries at different time points have shown. When hypothermia is used, hospitals go with the guidelines quite strictly with respect to indication, duration of treatment and target temperature. This strengthens the importance of guidelines in the process to implement new therapeutic options. However, although a recent study still promotes a strict target temperature management it questions the need for a markedly reduced target temperature of 33°C. It remains to be elucidated how this study will affect the daily routine in the hospitals and most interestingly how this study will change the coming guidelines in 2015. PMID:26261928

  14. Improved Therapeutic Benefits by Combining Physical Cooling With Pharmacological Hypothermia After Severe Stroke in Rats

    PubMed Central

    Lee, Jin Hwan; Wei, Ling; Gu, Xiaohuan; Won, Soonmi; Wei, Zheng Zachory; Dix, Thomas A.

    2016-01-01

    Background and Purpose— Therapeutic hypothermia is a promising strategy for treatment of acute stroke. Clinical translation of therapeutic hypothermia, however, has been hindered because of the lack of efficiency and adverse effects. We sought to enhance the clinical potential of therapeutic hypothermia by combining physical cooling (PC) with pharmacologically induced hypothermia after ischemic stroke. Methods— Wistar rats were subjected to 90-minute middle cerebral artery occlusion by insertion of an intraluminal filament. Mild-to-moderate hypothermia was induced 120 minutes after the onset of stroke by PC alone, a neurotensin receptor 1 (NTR1) agonist HPI-201 (formally ABS-201) alone or the combination of both. The outcomes of stroke were evaluated at 3 and 21 days after stroke. Results— PC or HPI-201 each showed hypothermic effect and neuroprotection in stroke rats. The combination of PC and HPI-201 exhibited synergistic effects in cooling process, reduced infarct formation, cell death, and blood-brain barrier damages and improved functional recovery after stroke. Importantly, coapplied HPI-201 completely inhibited PC-associated shivering and tachycardia. Conclusions— The centrally acting hypothermic drug HPI-201 greatly enhanced the efficiency and efficacy of conventional PC; this combined cooling therapy may facilitate clinical translation of hypothermic treatment for stroke. PMID:27301934

  15. Prevention of perioperative hypothermia in plastic surgery.

    PubMed

    Young, V Leroy; Watson, Marla E

    2006-01-01

    While inadvertent perioperative hypothermia has received serious attention in many surgical specialties, few discussions of hypothermia have been published in the plastic surgery literature. This article reviews the physiology of thermoregulation, describes how both general and regional anesthesia alter the normal thermoregulatory mechanisms, indicates risk factors particularly associated with hypothermia, and discusses the most effective current methods for maintaining normothermia. Hypothermia is typically defined as a core body temperature of /=36.5 degrees C is maintained. Unless preventive measures are instituted, inadvertent hypothermia occurs in 50% to 90% of surgical patients, even those undergoing relatively short procedures lasting one to one-and-a-half hours. During either general or regional anesthesia, a patient's natural behavioral and autonomic responses to cold are unavailable or impaired, and the combination of general and neuraxial anesthesia produces the highest risk for inadvertent perioperative hypothermia. Unless hypothermia is prevented, the restoration of normothermia can take more than 4 hours once anesthesia is stopped. Consequences of hypothermia are serious and affect surgical outcomes in plastic surgery patients. Potential complications include morbid cardiac events, coagulation disorders and blood loss, increased incidence of surgical wound infection, postoperative shivering, longer hospital stays, and increased costs associated with surgery. Measures for preventing hypothermia are emphasized in this article, especially those proven most effective in prospective and controlled clinical studies. Perhaps the most important step in maintaining normothermia is to prewarm patients in the preoperative area with forced-air heating systems. Intraoperative warming with forced-air and fluid warming are also essential. Other strategies

  16. Platelet-activating factor is a potent pyrogen and cryogen, but it does not mediate lipopolysaccharide fever or hypothermia.

    PubMed

    Steiner, Alexandre A; Romanovsky, Andrej A

    2015-01-01

    We examined whether platelet-activating factor (PAF) and its receptor mediate lipopolysaccharide (LPS)-induced fever and hypothermia in rats. Two highly potent, structurally distinct antagonists of the PAF receptor, CV6209 and WEB2086, were used. At a neutral ambient temperature (Ta) of 30ºC, administration of LPS at a low (10 μg/kg, i.v.) or high (1,000 μg/kg, i.v.) dose resulted in fever. The response to the high dose was turned into hypothermia at a subneutral Ta of 22ºC. Neither LPS-induced fever nor hypothermia was affected by pretreatment with CV6209 (5 mg/kg, i.v.) or WEB2086 (5 mg/kg, i.v.). However, both PAF antagonists were efficacious in blocking the thermoregulatory response caused by PAF (334 pmol/kg/min, 1 h, i.v.), regardless of whether the response was a fever (at 30ºC) or hypothermia (at 22ºC). Additional experiments showed that the thermoregulatory responses to LPS and PAF are also distinct in terms of their mediation by prostaglandins. Neither PAF fever nor PAF hypothermia was affected by pretreatment with the cyclooxygenase-2 inhibitor SC236 (5 mg/kg, i.p.), which is known to abrogate LPS fever. The responses to PAF were also unaffected by pretreatment with the cyclooxygenase-1 inhibitor SC560 (5 mg/kg, i.p.), which is known to attenuate LPS hypothermia. In conclusion, PAF infusion at a picomolar dose causes fever at thermoneutrality but hypothermia in a subthermoneutral environment, both responses being dependent on the PAF receptor and independent of prostaglandins. However, the PAF receptor does not mediate LPS-induced fever or hypothermia, thus challenging the dogma that PAF is an upstream mediator of responses to LPS. PMID:27227073

  17. Platelet-activating factor is a potent pyrogen and cryogen, but it does not mediate lipopolysaccharide fever or hypothermia

    PubMed Central

    Steiner, Alexandre A; Romanovsky, Andrej A

    2015-01-01

    We examined whether platelet-activating factor (PAF) and its receptor mediate lipopolysaccharide (LPS)-induced fever and hypothermia in rats. Two highly potent, structurally distinct antagonists of the PAF receptor, CV6209 and WEB2086, were used. At a neutral ambient temperature (Ta) of 30ºC, administration of LPS at a low (10 μg/kg, i.v.) or high (1,000 μg/kg, i.v.) dose resulted in fever. The response to the high dose was turned into hypothermia at a subneutral Ta of 22ºC. Neither LPS-induced fever nor hypothermia was affected by pretreatment with CV6209 (5 mg/kg, i.v.) or WEB2086 (5 mg/kg, i.v.). However, both PAF antagonists were efficacious in blocking the thermoregulatory response caused by PAF (334 pmol/kg/min, 1 h, i.v.), regardless of whether the response was a fever (at 30ºC) or hypothermia (at 22ºC). Additional experiments showed that the thermoregulatory responses to LPS and PAF are also distinct in terms of their mediation by prostaglandins. Neither PAF fever nor PAF hypothermia was affected by pretreatment with the cyclooxygenase-2 inhibitor SC236 (5 mg/kg, i.p.), which is known to abrogate LPS fever. The responses to PAF were also unaffected by pretreatment with the cyclooxygenase-1 inhibitor SC560 (5 mg/kg, i.p.), which is known to attenuate LPS hypothermia. In conclusion, PAF infusion at a picomolar dose causes fever at thermoneutrality but hypothermia in a subthermoneutral environment, both responses being dependent on the PAF receptor and independent of prostaglandins. However, the PAF receptor does not mediate LPS-induced fever or hypothermia, thus challenging the dogma that PAF is an upstream mediator of responses to LPS. PMID:27227073

  18. [Recent treatment of postischaemic anoxic brain damage after cardiac arrest by using therapeutic hypothermia].

    PubMed

    Andjelić, Sladjana

    2008-01-01

    Organ injury caused by ischaemia and anoxia during prolonged cardiac arrest is compounded by reperfusion injury that occurs when spontaneous circulation is restored. Mild hypothermia (32-35 degrees C) is neuroprotective through several mechanisms, including suppression of apoptosis, reduced production of excitotoxins and free radicals, and anti-inflammatory actions. Experimental studies show that hypothermia is more effective the earlier it is started after return of spontaneous circulation (ROSC). Two randomised clinical trials show improved survival and neurological outcome in adults who remained comatose after initial resuscitation from prehospital VF cardiac arrest, and who were cooled after ROSC. Different strategies can be used to induce hypothermia. Optimal timing of therapeutic hypothermia for cardiac ischaemia is unknown. In patients who failed to respond to standard cardiopulmonary resuscitation, intra-arrest cooling using ice-cold intravenous (i.v.) fluid improved the chance of survival. Recently, fasudil, a Rho kinase inhibitor, was reported to prevent cerebral ischaemia in vivo by increasing cerebral blood flow and inhibiting inflammatory responses. In future, two different kinds of protective therapies, BCL-2 overexpression and hypothermia,will both inhibit aspects of apoptotic cell death cascades, and that combination treatment can prolong the temporal "therapeutic window" for gene therapy. PMID:19069351

  19. Neuroprotective effect of epidural hypothermia after spinal cord lesion in rats

    PubMed Central

    Barbosa, Marcello Oliveira; Cristante, Alexandre Fogaça; dos Santos, Gustavo Bispo; Ferreira, Ricardo; Marcon, Raphael Martus; de Barros Filho, Tarcisio Eloy Pessoa

    2014-01-01

    OBJECTIVES : To evaluate the neuroprotective effect of epidural hypothermia in rats subjected to experimental spinal cord lesion. METHODS: Wistar rats (n = 30) weighing 320-360 g were randomized to two groups (hypothermia and control) of 15 rats per group. A spinal cord lesion was induced by the standardized drop of a 10-g weight from a height of 2.5 cm, using the New York University Impactor, after laminectomy at the T9-10 level. Rats in the hypothermia group underwent epidural hypothermia for 20 minutes immediately after spinal cord injury. Motor function was assessed for six weeks using the Basso, Beattie and Bresnahan motor scores and the inclined plane test. At the end of the final week, the rats' neurological status was monitored by the motor evoked potential test and the results for the two groups were compared. RESULTS: Analysis of the Basso, Beattie and Bresnahan scores obtained during the six-week period indicated that there were no significant differences between the two groups. There was no significant difference between the groups in the inclined plane test scores during the six-week period. Furthermore, at the end of the study, the latency and amplitude values of the motor evoked potential test were not significantly different between the two groups. CONCLUSION: Hypothermia did not produce a neuroprotective effect when applied at the injury level and in the epidural space immediately after induction of a spinal cord contusion in Wistar rats. PMID:25141116

  20. Inadvertant hypothermia and active warming for surgical patients.

    PubMed

    Tanner, Judith

    Inadvertant hypothermia is common among surgical patients and can result in serious complications. This article describes active warming systems which can be used preoperatively and intraoperatively to prevent hypothermia and maintain normothermia (normal body temperature). PMID:22067488

  1. Data on the gene expression of cardiomyocyte exposed to hypothermia.

    PubMed

    Zhang, Jian; Xue, Xiaodong; Xu, Yinli; Zhang, Yuji; Li, Zhi; Wang, Huishan

    2016-09-01

    Hypothermia is widely used in neurosurgery and cardiac surgeries. However, little is known about the underlying molecular mechanisms. We previously reported that the transcriptome responses of cardiomyocyte exposed to hypothermia, "The transcriptome responses of cardiomyocyte exposed to hypothermia" [4]. Herein, we provide the hypothermia inhibited proliferation of cardiomyocyte cells in vitro and the details of transcription factors in regulation of differentially expressed genes. PMID:27274530

  2. Free oscillation rheometry monitoring of haemodilution and hypothermia and correction with fibrinogen and factor XIII concentrates

    PubMed Central

    2013-01-01

    Background Haemodilution and hypothermia induce coagulopathy separately, but their combined effect on coagulation has not been widely studied. Fibrinogen concentrate can correct dilutional coagulopathy and has an additional effect when combined with factor XIII concentrate. However, their effect on dilutional coagulopathy concomitant with hypothermia has not been studied previously. Free oscillation rheometry – FOR (Reorox®) – is a novel viscoelastic haemostatic assay that has not been studied in this context before. Methods Blood from 10 healthy volunteers was diluted by 33% with hydroxyethyl starch or Ringer’s acetate solutions. Effects of fibrinogen added in vitro with and without factor XIII were studied at 33°C and 37°C. Coagulation velocity (coagulation time) and clot strength (elasticity) were assessed with FOR. Coagulation was initiated in vitro with thromboplastin alone, or thromboplastin plus a platelet inhibitor. Results Hydroxyethyl starch increased the coagulation time and decreased clot strength significantly more than Ringer’s acetate solution, both in the presence and absence of a platelet inhibitor. There was a significant interaction between haemodilution with hydroxyethyl starch and hypothermia, resulting in increased coagulation time. After addition of fibrinogen, coagulation time shortened and elasticity increased, with the exception of fibrinogen-dependent clot strength (i.e., elasticity in the presence of a platelet inhibitor) after hydroxyethyl starch haemodilution. Factor XIII had an additional effect with fibrinogen on fibrinogen-dependent clot strength in blood diluted with Ringer’s acetate solution. Hypothermia did not influence any of the coagulation factor effects. Conclusions Both haemodilution and mild hypothermia impaired coagulation. Coagulopathy was more pronounced after haemodilution with hydroxyethyl starch than with Ringer’s acetate. Addition of fibrinogen with factor XIII was unable to reverse hydroxyethyl

  3. Hypothermia increases interleukin-6 and interleukin-10 in juvenile endotoxemic mice

    PubMed Central

    Stewart, Corrine R.; Landseadel, Jessica P.; Gurka, Matthew J.; Fairchild, Karen D.

    2013-01-01

    Objective To develop a juvenile mouse model to establish effects of in vivo hypothermia on expression of the inflammation-modulating cytokines tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-10. Although induced hypothermia is neuroprotective in some patients, the mechanisms of protection are not well understood and concerns remain over potential detrimental effects, particularly in the setting of infection. We previously showed that in vitro hypothermia increases production of tumor necrosis factor-α and interleukin-1β in lipopolysaccharide-treated monocytes. Design Laboratory investigation. Setting Research laboratory. Subjects Juvenile (4-wk) male C57BL/6 mice. Interventions Mice were given chlorpromazine to suspend thermoregulation and lipopolysaccharide to stimulate cytokine production. Core temperature was maintained at 32°C or 37°C for 6 hrs by adjusting environmental temperature. In separate experiments, lipopolysaccharide-treated mice were kept in a cooling chamber without chlorpromazine treatment. Measurements and Main Results Plasma and organs were collected for cytokine quantitation. Chlorpromazine-treated hypothermic mice had 2.3-fold and 1.8-fold higher plasma interleukin-6 and interleukin-10 levels at 6 hrs compared with identically treated normothermic mice (p < .05), whereas plasma tumor necrosis factor-α and interleukin-1β were not significantly different at 2 hrs or 6 hrs. Liver tumor necrosis factor-α and interleukin-6 were significantly higher in hypothermic vs. normothermic mice, but lung and brain cytokines were not different. Lipopolysaccharide-treated mice kept in a cooling chamber without chlorpromazine treatment developed varying degrees of hypothermia with associated increases in plasma interleukin-6 and interleukin-10. A nonspecific marker of stress (plasma corticosterone) was not affected by hypothermia in lipopolysaccharide-treated mice. Conclusion Further studies are necessary to determine the

  4. Hypothermia, torpor and the fundamental importance of understanding the central control of thermoregulation

    PubMed Central

    Tupone, Domenico; Morrison, Shaun

    2014-01-01

    Activation of central adenosine A1 receptors in the rat, a non-hibernating species, mimics the physiological characteristics of torpor and could thus represent a basis for the development of pharmacological approaches to induce therapeutic hypothermia in pathologies such as brain hemorrhage and ischemia, and to facilitate long-term space travel.

  5. N-Octanoyl Dopamine Treatment of Endothelial Cells Induces the Unfolded Protein Response and Results in Hypometabolism and Tolerance to Hypothermia

    PubMed Central

    Stamellou, Eleni; Fontana, Johann; Wedel, Johannes; Ntasis, Emmanouil; Sticht, Carsten; Becker, Anja; Pallavi, Prama; Wolf, Kerstin; Krämer, Bernhard K.; Hafner, Mathias; van Son, Willem J.; Yard, Benito A.

    2014-01-01

    Aim N-acyl dopamines (NADD) are gaining attention in the field of inflammatory and neurological disorders. Due to their hydrophobicity, NADD may have access to the endoplasmic reticulum (ER). We therefore investigated if NADD induce the unfolded protein response (UPR) and if this in turn influences cell behaviour. Methods Genome wide gene expression profiling, confirmatory qPCR and reporter assays were employed on human umbilical vein endothelial cells (HUVEC) to validate induction of UPR target genes and UPR sensor activation by N-octanoyl dopamine (NOD). Intracellular ATP, apoptosis and induction of thermotolerance were used as functional parameters to assess adaptation of HUVEC. Results NOD, but not dopamine dose dependently induces the UPR. This was also found for other synthetic NADD. Induction of the UPR was dependent on the redox activity of NADD and was not caused by selective activation of a particular UPR sensor. UPR induction did not result in cell apoptosis, yet NOD strongly impaired cell proliferation by attenuation of cells in the S-G2/M phase. Long-term treatment of HUVEC with low NOD concentration showed decreased intracellular ATP concentration paralleled with activation of AMPK. These cells were significantly more resistant to cold inflicted injury. Conclusions We provide for the first time evidence that NADD induce the UPR in vitro. It remains to be assessed if UPR induction is causally associated with hypometabolism and thermotolerance. Further pharmacokinetic studies are warranted to address if the NADD concentrations used in vitro can be obtained in vivo and if this in turn shows therapeutic efficacy. PMID:24926788

  6. Intra-arrest Hypothermia: Both Cold Liquid Ventilation with Perfluorocarbons and Cold Intravenous Saline Rapidly Achieve Hypothermia, but Only Cold Liquid Ventilation Improves Resumption of Spontaneous Circulation

    PubMed Central

    Riter, Henry G.; Brooks, Leonard A.; Pretorius, Andrew M.; Ackermann, Laynez W.; Kerber, Richard E.

    2009-01-01

    Background Rapid intra-arrest induction of hypothermia using total liquid ventilation (TLV) with cold perfluorocarbons improves resuscitation outcome from ventricular fibrillation (VF). Cold saline intravenous infusion during cardiopulmonary resuscitation (CPR) is a simpler method of inducing hypothermia. We compared these 2 methods of rapid hypothermia induction for cardiac resuscitation. Methods Three groups of swine were studied: cold preoxygenated TLV (TLV, n=8), cold intravenous saline infusion (S, n=8), and control (C, n=8). VF was electrically induced. Beginning at 8 minutes of VF, TLV and S animals received 3 minutes of cold TLV or rapid cold saline infusion. After 11 minutes of VF, all groups received standard air ventilation and closed chest massage. Defibrillation was attempted after 3 minutes of CPR (14 minutes of VF). The end point was resumption of spontaneous circulation (ROSC). Results Pulmonary arterial (PA) temperature decreased after 1 minute of CPR from 37.2°C to 32.2°C in S and from 37.1°C to 34.8°C in TLV (S or TLV vs. C p<0.0001). Coronary perfusion pressure (CPP) was higher in TLV than S animals during the initial 3 minutes of CPR. Arterial pO2 was higher in the preoxygenated TLV animals. ROSC was achieved in 7 of 8 TLV, 2 of 8 S, and 1 of 8 C (TLV vs. C, p=0.03). Conclusions Moderate hypothermia was achieved rapidly during VF and CPR using both cold saline infusion and cold TLV, but ROSC was higher than control only in cold TLV animals, probably due to better CPP and pO2. The method by which hypothermia is achieved influences ROSC. PMID:19249149

  7. Dose-dependent effects of levetiracetam after hypoxia and hypothermia in the neonatal mouse brain.

    PubMed

    Strasser, Katja; Lueckemann, Laura; Kluever, Verena; Thavaneetharajah, Sinthuya; Hoeber, Daniela; Bendix, Ivo; Fandrey, Joachim; Bertsche, Astrid; Felderhoff-Mueser, Ursula

    2016-09-01

    Perinatal asphyxia to the developing brain remains a major cause of morbidity. Hypothermia is currently the only established neuroprotective treatment available for term born infants with hypoxic-ischemic encephalopathy, saving one in seven to eight infants from developing severe neurological deficits. Therefore, additional treatments with clinically applicable drugs are indispensable. This study investigates a potential additive neuroprotective effect of levetiracetam combined with hypothermia after hypoxia-induced brain injury in neonatal mice. 9-day-old C57BL/6-mice (P9) were subjected either to acute hypoxia or room-air. After 90min of systemic hypoxia (6% O2), pups were randomized into six groups: 1) vehicle, 2) low-dose levetiracetam (LEV), 3) high-dose LEV, 4) hypothermia (HT), 5) HT combined with low-dose LEV and 6) HT combined with high-dose LEV. Pro-apoptotic factors, neuronal structures, and myelination were analysed by histology and on protein level at appropriate time points. On P28 to P37 long-term outcome was assessed by neurobehavioral testing. Hypothermia confers acute and long-term neuroprotection by reducing apoptosis and preservation of myelinating oligodendrocytes and neurons in a model of acute hypoxia in the neonatal mouse brain. Low-dose LEV caused no adverse effects after neonatal hypoxic brain damage treated with hypothermia whereas administration of high-dose LEV alone or in combination with hypothermia increased neuronal apoptosis after hypoxic brain injury. LEV in low- dosage had no additive neuroprotective effect following acute hypoxic brain injury. PMID:27216570

  8. Hypothermia and the Elderly: Perceptions and Behaviors.

    ERIC Educational Resources Information Center

    Avery, Carol E.; Pestle, Ruth E.

    1987-01-01

    Interviewed 381 older adults participating in Area Agency on Aging meal programs in Florida. Found that only 10 percent were aware of dangers of accidental hypothermia. Many low-income elderly are vulnerable to cold because of poorly insulated homes, inadequate heating, and lack of warm clothing. States need initiatives to increase comfort levels…

  9. [Hypothermia in people in situations of precarity].

    PubMed

    Bernard, Serge

    2011-05-01

    Human beings are physiologically warm blooded. Confronted with extreme cold, they become subject to hypothermia. Between a mountain climber and a person living in the street, the functions of resistance to a drop in external temperature are not the same. Studies on this subject remain to be carried out. PMID:21717680

  10. Ultrasonic vocalization by rat pups during recovery from deep hypothermia.

    PubMed

    Hofer, M A; Shair, H N

    1992-11-01

    Vocalization in the ultrasonic range (USV) has been reported to occur in young rodents in response to isolation, novelty, handling, and cold. Heretofore these calls have been known to occur only in alert, attentive, or emotionally aroused animals. These studies describe the emission of USV by comatose 9- to 10-day-old rat pups during recovery from deep hypothermia. Calling began at 15-18 degrees C core temperature while pups were virtually unresponsive to stimulation. Experimental results describe the patterns of call production in relation to respiration, cardiac function, colonic temperature, and brown adipose tissue thermogenesis. These vocalizations were 32-42 kHz in frequency, reached peak rates of 50/min at 23 degrees C, and were eliminated by laryngeal denervation, thus resembling isolation-induced vocalizations. However, contact with their dams failed to reduce call rates until pups had warmed above 25 degrees C. Newborn and weanling pups also emitted USV in deep hypothermia, but no USV were observed in pups recovering from general anesthesia. The possible functions and evolution of this behavior are discussed. PMID:1459345

  11. Hypometabolism and hypothermia in the rat model of endotoxic shock: independence of circulatory hypoxia

    PubMed Central

    Corrigan, Joshua J; Fonseca, Monique T; Flatow, Elizabeth A; Lewis, Kevin; Steiner, Alexandre A

    2014-01-01

    We tested the hypothesis that development of hypothermia instead of fever in endotoxic shock is consequential to hypoxia. Endotoxic shock was induced by bacterial lipopolysaccharide (LPS, 500 μg kg−1 i.v.) in rats at an ambient temperature of 22°C. A β3-adrenergic agonist known to activate metabolic heat production, CL316,243, was employed to evaluate whether thermogenic capacity could be impaired by the fall in oxygen delivery () during endotoxic shock. This possibility was rejected as CL316,243 (0.15 mg kg−1 i.v.) evoked similar rises in oxygen consumption () in the presence and absence of endotoxic shock. Next, to investigate whether a less severe form of circulatory hypoxia could be triggering hypothermia, the circulating volume of LPS-injected rats was expanded using 6% hetastarch with the intention of improving tissue perfusion and alleviating hypoxia. This intervention attenuated not only the fall in arterial pressure induced by LPS, but also the associated falls in and body temperature. These effects, however, occurred independently of hypoxia, as they were not accompanied by any detectable changes in NAD+/NADH ratios. Further experimentation revealed that even the earliest drops in cardiac output and during endotoxic shock did not precede the reduction in that brings about hypothermia. In fact, and fell in such a synchrony that the / ratio remained unaffected. Only when hypothermia was prevented by exposure to a warm environment (30°C) did an imbalance in the / ratio become evident, and such an imbalance was associated with reductions in the renal and hypothalamic NAD+/NADH ratios. In conclusion, hypometabolism and hypothermia in endotoxic shock are not consequential to hypoxia but serve as a pre-emptive strategy to avoid hypoxia in this model. PMID:24951620

  12. Posttraumatic hypothermia increases doublecortin expressing neurons in the dentate gyrus after traumatic brain injury in the rat

    PubMed Central

    Bregy, Amade; Nixon, Ryan; Lotocki, George; Alonso, Ofelia F.; Atkins, Coleen M.; Tsoulfas, Pantelis; Bramlett, Helen M.; Dietrich, W. Dalton

    2012-01-01

    Previous studies have demonstrated that moderate hypothermia reduces histopathological damage and improves behavioral outcome after experimental traumatic brain injury (TBI). Further investigations have clarified the mechanisms underlying the beneficial effects of hypothermia by showing that cooling reduces multiple cell injury cascades. The purpose of this study was to determine whether hypothermia could also enhance endogenous reparative processes following TBI such as neurogenesis and the replacement of lost neurons. Male Sprague-Dawley rats underwent moderate fluid-percussion brain injury and then were randomized into normothermia (37°C) or hypothermia (33°C) treatment. Animals received injections of 5-bromo-2′-deoxyuridine (BrdU) to detect mitotic cells after brain injury. After 3 or 7 days, animals were perfusion-fixed and processed for immunocytochemistry and confocal analysis. Sections were stained for markers selective for cell proliferation (BrdU), neuroblasts and immature neurons (doublecortin), and mature neurons (NeuN) and then analyzed using non-biased stereology to quantify neurogenesis in the dentate gyrus (DG). At 7 days after TBI, both normothermic and hypothermic TBI animals demonstrated a significant increase in the number of BrdU-immunoreactive cells in the DG as compared to sham-operated controls. At 7 days post-injury, hypothermia animals had a greater number of BrdU (ipsilateral cortex) and doublecortin (ipsilateral and contralateral cortex) immunoreactive cells in the DG as compared to normothermia animals. Because adult neurogenesis following injury may be associated with enhanced functional recovery, these data demonstrate that therapeutic hypothermia sustains the increase in neurogenesis induced by TBI and this may one of the mechanisms by which hypothermia promotes reparative strategies in the injured nervous system. PMID:22197046

  13. Management of neonatal morbidities during hypothermia treatment.

    PubMed

    Sarkar, Subrata; Barks, John

    2015-04-01

    Although the primary goal of therapeutic hypothermia is to improve the neurodevelopmental outcome in asphyxiated infants, optimal management of the full range of multi-organ system complications typically presented by such infants during cooling treatment is necessary for improvement of the overall outcome. For this reason, adequate knowledge of how cooling affects all organ systems of asphyxiated infants with multi-organ hypoxic-ischemic injury is essential. Adequate diagnostic resources, readily available subspecialty consultant services and trained multidisciplinary staff to monitor and manage multi-organ system complications in asphyxiated infants during therapeutic cooling must be ensured during implementation of a cooling program. As therapeutic hypothermia is being used more widely, centers should consider participation in national or international benchmarking of outcomes and short-term adverse events during cooling to facilitate continuous quality improvement efforts. PMID:25701292

  14. [Management of peri-operative hypothermia].

    PubMed

    Fernández-Meré, L A; Alvarez-Blanco, M

    2012-01-01

    Hypothermia (body temperature under 36°C) is the thermal disorder most frequently found in surgical patients, but should be avoided as a means of reducing morbidity and costs. Temperature should be considered as a vital sign and all staff involved in the care of surgical patients must be aware that it has to be maintained within normal limits. Maintaining body temperature is the result, as in any other system, of the balance between heat production and heat loss. Temperature regulation takes place through a system of positive and negative feedback in the central nervous system, being developed in three phases: thermal afferent, central regulation and efferent response. Prevention is the best way to ensure a normal temperature. The active warming of the patient during surgery is mandatory. Using warm air is the most effective, simple and cheap way to prevent and treat hypothermia. PMID:22789615

  15. The small chill: mild hypothermia for cardioprotection?

    PubMed

    Tissier, Renaud; Chenoune, Mourad; Ghaleh, Bijan; Cohen, Michael V; Downey, James M; Berdeaux, Alain

    2010-12-01

    Reducing the heart's temperature by 2-5°C is a potent cardioprotective treatment in animal models of coronary artery occlusion. The anti-infarct benefit depends upon the target temperature and the time at which cooling is instituted. Protection primarily results from cooling during the ischaemic period, whereas cooling during reperfusion or beyond offers little protection. In animal studies, protection is proportional to both the depth and duration of cooling. An optimal cooling protocol must appreciably shorten the normothermic ischaemic time to effectively salvage myocardium. Patients presenting with acute myocardial infarction could be candidates for mild hypothermia since the current door-to-balloon time is typically 90 min. But they would have to be cooled quickly shortly after their arrival. Several strategies have been proposed for ultra-fast cooling, but most like liquid ventilation and pericardial perfusion are too invasive. More feasible strategies might include cutaneous cooling, peritoneal lavage with cold solutions, and endovascular cooling with intravenous thermodes. This last option has been investigated clinically, but the results have been disappointing possibly because the devices lacked capacity to cool the patient quickly or cooling was not implemented soon enough. The mechanism of hypothermia's protection has been assumed to be energy conservation. However, whereas deep hypothermia clearly preserves ATP, mild hypothermia has only a modest effect on ATP depletion during ischaemia. Some evidence suggests that intracellular signalling pathways might be responsible for the protection. It is unknown how cooling could trigger these pathways, but, if true, then it might be possible to duplicate cooling's protection pharmacologically. PMID:20621922

  16. Proteomic analysis of global protein expression changes in the endothelin-1 rat model for cerebral ischemia: rescue effect of mild hypothermia.

    PubMed

    Zgavc, Tine; Hu, Tjing-Tjing; Van de Plas, Babs; Vinken, Mathieu; Ceulemans, An-Gaëlle; Hachimi-Idrissi, Said; Sarre, Sophie; Michotte, Yvette; Arckens, Lutgarde

    2013-11-01

    Mild hypothermia is a promising neuroprotective therapy in stroke management. However, little is known about its effects on the global protein expression patterns in brain regions affected by ischemic stroke. We investigated protein expression changes associated with the neuroprotective effects of hypothermia via a functional proteomics approach through the analysis of the core (striatum) and the penumbra (cortex) after an ischemic insult in rats induced by endothelin-1 (Et-1). Functional outcome, infarct volume and related global protein expression changes were assessed 24h after the insult using two-dimensional difference gel electrophoresis. Mild hypothermia, induced 20 min after endothelin-1 infusion, improved the neurological outcome, reflected by a 36% reduction in infarct volume and a significantly better neurological deficit score. Hypothermia was typically associated with opposite protein expression changes inthe cortex to those induced by stroke under normothermic conditions, but not in the striatum. The main cellular processes rescued by hypothermia and potentially involved in the protection of the cortex are cellular assembly and organization, followed by cell signaling, thereby confirming that hypothermia is neuroprotective through multiple molecular and cellular pathways. PMID:23927863

  17. GABAB receptors as a common target for hypothermia and spike and wave seizures: intersecting mechanisms of thermoregulation and absence epilepsy.

    PubMed

    Ostojić, Z S; Ilić, T V; Vesković, S M; Andjus, P R

    2013-05-15

    In the current study the link among the γ-hydroxybutyrate (GHB)/pentylenetetrazole (PTZ)-induced absence-like seizures and concomitant decreases in the core temperature, as well as electroencephalographic (EEG) activity during rewarming from deep hypothermia produced by a drug-free protocol were investigated. During the rewarming period after deep cooling, most Wistar rats suffered from bilaterally synchronous spike and waves with no or mild behavioral correlates. Spike and wave seizures were temperature-dependent and were initially registered when body temperature (Tb) reached 25-27°C, but mostly during the mild hypothermia of 0.3-1.3°C (Tb of 36.3-37.3°C). In chemical absence models, spike and wave discharges were also closely accompanied by mild systemic hypothermia, as both PTZ- and GHB-induced temperature decreases ranged from about 1-1.4°C respectively, together with EEG markers of absence activity. Thus, throughout the different experimental designs, the occurrence of spike and wave discharges was always related to a mild (0.3-1.4°C) decrease of Tb. Benzodiazepine diazepam as the GABAA-positive allosteric modulator and CGP 62349 as the selective antagonist of GABAB receptors were used to determine if their well-known anticonvulsant properties also affect hypothermia elicited by these drugs. Finally, during the course of spontaneous rewarming from deep hypothermia, another selective GABAB-blocking agent, CGP 35348, was used to elucidate if GABAB inhibitory system could be critically implicated in the generation of hypothermia-dependent spike and waves. Diazepam prevented both the PTZ-induced hypothermia and electrographic absence seizures, but these two beneficial effects did not occur in the GHB model. Even though diazepam delayed GHB-induced maximal temperature decrease, the GHB effects remained highly significant. The GABAB antagonist CGP 62349 completely prevented hypothermia as well as absence seizures in both chemical models. Likewise, spike and

  18. [Severe accidental hypothermia in an elderly woman].

    PubMed

    Knobel, B; Mikhlin, A

    2001-11-01

    Profound hypothermia (core temperature of less than 28 degrees C) is a life threatening state and a medical emergency associated with a high mortality rate. The prognosis depends on underlying diseases, advanced or very early age, the duration prior to treatment, the degree of hemodynamic deterioration, and especially, the methods of treatment, including active external or internal rewarming. This is a case study of an 80-year-old female patient with severe accidental hypothermia (core temperature 27 degrees C). She was found in her home lying immobile on the cold floor after a fall. The patient was in a profound coma with cardiocirculatory collapse, and the medical staff treating her was inclined to pronounce her deceased. On her arrival at the hospital, she was resuscitated, put on a respirator and actively warmed. Very severe metabolic disorders were found, including a marked metabolic acidosis composed of diabetic ketoacidosis (she had suffered from insulin treated type 2 diabetes mellitus) and lactic acidosis with a very high anion gap (42) and a hyperosmotic state (blood glucose 1202 mg/dl). There were pathognomonic electrocardiographic abnormalities, J-wave of Osborn and prolonged repolarization. Slow atrial fibrillation with a ventricular response of 30 bpm followed by a nodal rhythm of 12 bpm and reversible cardiac arrest were recorded. The pulse and blood pressure were unobtainable. Despite the successful resuscitation and hemodynamic and cognitive improvement, rhabdomyolysis (CKP 6580 u/L), renal failure and hepatic damage developed. She was extubated and treated with intravenous fluids containing dopamine, bicarbonate, insulin and antibiotics. Her medical condition gradually improved, and she was discharged clear minded, functioning very well and independent. Renal and liver tests returned eventually to normal limits. Progressive bradycardia, hypotension and death due to ventricular fibrillation or asystole commonly occur during severe hypothermia

  19. Endovascular Cooling Method for Hypothermia in Injured Swine.

    PubMed

    Arnaud, Françoise; Haque, Ashraful; Solomon, Daniel; Kim, Robert B; Pappas, Georgina; Scultetus, Anke H; Auker, Charles; McCarron, Richard

    2016-06-01

    We evaluated an endovascular cooling method to modulate core temperature in trauma swine models with and without fluid support. Anesthetized swine (N = 80) were uninjured (SHAM) or injured through a bone fracture plus soft tissue injury or an uncontrolled hemorrhage and then subdivided to target body temperatures of 38°C (normothermia) or 33°C (hypothermia) by using a Thermogard endovascular cooling device (Zoll Medical). Temperature regulation began simultaneously at onset of injury (T0). Body temperatures were recorded from a rectal probe (Rec Temp) and from a central pulmonary artery catheter (PA Temp). At T15, swine received 500 mL IV Hextend over 30 minutes or no treatment (NONE) with continued monitoring until 3 hours from injury. Hypothermia was attained in 105 ± 39 minutes, at a cooling rate of -0.061°C ± 0.007°C/min for NONE injury groups. Postinjury Hextend administration resulted in faster cooling (-0.080°C ± 0.006°C/min); target temperature was reached in 83 ± 11 minutes (p < 0.05). During active cooling, body temperature measured by the PA Temp was significantly cooler than the Rec Temp due to the probe's closer proximity to the blood-cooling catheter balloons (p < 0.05). This difference was smaller in SHAM and fluid-supported injury groups (1.1°C ± 0.4°C) versus injured NONE groups (2.1°C ± 0.3°C). Target temperatures were correctly maintained thereafter in all groups. In normothermia groups, there was a small initial transient overshoot to maintain 38°C. Despite the noticeable difference between PA Temp and Rec Temp until target temperature was attained, this endovascular method can safely induce moderate hypothermia in anesthetized swine. However, likely due to their compromised hemodynamic state, cooling in hypovolemic and/or injured patients will be different from those without injury or those that also received fluids. PMID:26918281

  20. Mild hypothermia attenuates post-resuscitation brain injury through a V-ATPase mechanism in a rat model of cardiac arrest.

    PubMed

    Zhang, J C; Lu, W; Xie, X M; Pan, H; Wu, Z Q; Yang, G T

    2016-01-01

    Although therapeutic hypothermia is an effective treatment for post-resuscitation brain injury after cardiac arrest (CA), the underlying mechanism remains unclear. Vacuolar H(+)-ATPase (V-ATPase) plays a key role in cellular adaption to a hypoxic environment. This study sought to evaluate the effect of mild hypothermia on V-ATPase and its involvement in neuroprotection after CA. Male Sprague-Dawley rats were subjected to a 6-min CA, resuscitated successfully, and then assigned to either the normothermia (NT) group or the hypothermia (HT) group. Rats were further divided into 2 subgroups based on the time of euthanasia, either 3 or 24 h after CA (NT-3 h, HT-3 h; NT-24 h, HT-24 h). Mild hypothermia was induced following CA and maintained at 33°C for 2 h. Neurologic deficit scores were used to determine the status of neurological function. Brain specimens were analyzed by TUNEL assay, western blotting, and immunohistochemistry. V-ATPase activity was estimated by subtracting total ATP hydrolysis from the bafilomycin-sensitive activity. Mild hypothermia improved the neurological outcome (HT-24 h: 34.3 ± 16.4 vs NT-24 h: 50.3 ± 17.4) and significantly decreased neurocyte apoptosis 24 h after resuscitation. Mild hypothermia significantly increased V0a1 compared to NT-3 h; V0a1 expression was associated with a decrease in the cleaved caspase 3 expression. These findings suggested that mild hypothermia inhibits CA-induced apoptosis in the hippocampus, which may be associated with reduced V-ATPase impairment. These data provide new insights into the protective effects of hypothermia in vivo. PMID:27323115

  1. Hypothermia improves disease manifestations in SMA mice via SMN augmentation.

    PubMed

    Tsai, Li-Kai; Chen, Chien-Lin; Tsai, Yi-Chieh; Ting, Chen-Hung; Chien, Yin-Hsio; Lee, Ni-Chong; Hwu, Wuh-Liang

    2016-02-15

    Spinal muscular atrophy (SMA) is a progressive motor neuron disease caused by a deficiency of survival motor neuron (SMN) protein. In this study, we evaluated the efficacy of intermittent transient hypothermia in a mouse model of SMA. SMA mice were exposed to ice for 50 s to achieve transient hypothermia (below 25°C) daily beginning on postnatal day 1. Neonatal SMA mice (Smn(-/-)SMN2(+/-)) who received daily transient hypothermia exhibited reduced motor neuron degeneration and muscle atrophy and preserved the architecture of neuromuscular junction when compared with untreated controls at day 8 post-treatment. Daily hypothermia also prolonged the lifespan, increased body weight and improved motor coordination in SMA mice. Quantitative polymerase chain reaction and western blot analyses showed that transient hypothermia led to an increase in SMN transcript and protein levels in the spinal cord and brain. In in vitro studies using an SMN knockdown motor neuron-like cell-line, transient hypothermia increased intracellular SMN protein expression and length of neurites, confirming the direct effect of hypothermia on motor neurons. These data indicate that the efficacy of intermittent transient hypothermia in improving outcome in an SMA mouse model may be mediated, in part, via an upregulation of SMN levels in the motor neurons. PMID:26647309

  2. Mechanisms of Hypothermia, Delayed Hyperthermia and Fever Following CNS Injury

    EPA Science Inventory

    Central nervous system (CNS) damage is often associated with robust body temperature changes, such as hypothermia and delayed hyperthermia. Hypothermia is one of the most common body temperature changes to CNS insults in rodents and is often associated with improved outcome. Alth...

  3. Therapeutic hypothermia and ischemic stroke: A literature review

    PubMed Central

    Tahir, Rizwan A.; Pabaney, Aqueel H.

    2016-01-01

    Background: Ischemic stroke is the fifth leading cause of death in the US. Clinical techniques aimed at helping to reduce the morbidity associated with stroke have been studied extensively, including therapeutic hypothermia. In this study, the authors review the literature regarding the role of therapeutic hypothermia in ischemic stroke to appreciate the evolution of hypothermia technology over several decades and to critically analyze several early clinical studies to validate its use in ischemic stroke. Methods: A comprehensive literature search was performed using PubMed and Google Scholar databases. Search terms included “hypothermia and ischemic stroke” and “therapeutic hypothermia.” A comprehensive search of the current clinical trials using clinicaltrials.gov was conducted using the keywords “stroke and hypothermia” to evaluate early and ongoing clinical trials utilizing hypothermia in ischemic stroke. Results: A comprehensive review of the evolution of hypothermia in stroke and the current status of this treatment was performed. Clinical studies were critically analyzed to appreciate their strengths and pitfalls. Ongoing and future registered clinical studies were highlighted and analyzed compared to the reported results of previous trials. Conclusion: Although hypothermia has been used for various purposes over several decades, its efficacy in the treatment of ischemic stroke is debatable. Several trials have proven its safety and feasibility; however, more robust, randomized clinical trials with large volumes of patients are needed to fully establish its utility in the clinical setting. PMID:27313963

  4. Gastric Mucosal Petechial Hemorrhages (Wischnewsky Lesions), Hypothermia, and Diabetic Ketoacidosis.

    PubMed

    Clark, Kenneth Howard; Stoppacher, Robert

    2016-09-01

    For more than 100 years since their initial description, gastric mucosal petechial hemorrhages have been discovered at autopsy in cases where environmental hypothermia was determined to be the cause of death. Although these lesions are frequently seen in deaths caused by environmental hypothermia, they can also be seen in cases where hypothermia is not implicated; however, this has been seldom described. We present a series of autopsy cases where hypothermia has been conclusively ruled out as a cause of death, in which Wischnewsky lesions are found. In all of these cases, diabetic ketoacidosis (DKA) was determined to be the proximate cause of death, as confirmed through clinical history, laboratory analysis, and absence of other anatomic or toxicological findings. We provide a mechanism of Wischnewsky lesion formation and how that mechanism relates to both hypothermia and ketoacidosis. Our data show that gastric mucosal petechial hemorrhages are not specific for hypothermia-related deaths, and are likely indicative of a state in which hypothermia and DKA have a common underlying pathophysiology, most likely a coagulopathy. Our data also illustrate that in autopsy cases where Wischnewsky lesions are found, DKA should be seriously considered as the underlying cause of death, particularly in the absence of indications of environmental hypothermia. PMID:27356011

  5. Fever and hypothermia in systemic inflammation: recent discoveries and revisions.

    PubMed

    Romanovsky, Andrej A; Almeida, Maria C; Aronoff, David M; Ivanov, Andrei I; Konsman, Jan P; Steiner, Alexandre A; Turek, Victoria F

    2005-01-01

    Systemic inflammation is accompanied by changes in body temperature, either fever or hypothermia. Over the past decade, the rat and mouse have become the predominant animal models, and new species-specific tools (recombinant antibodies and other proteins) and genetic manipulations have been applied to study fever and hypothermia. Remarkable progress has been achieved. It has been established that the same inflammatory agent can induce either fever or hypothermia, depending on several factors. It has also been established that experimental fevers are generally polyphasic, and that different mechanisms underlie different febrile phases. Signaling mechanisms of the most common pyrogen used, bacterial lipopolysaccharide (LPS), have been found to involve the Toll-like receptor 4. The roles of cytokines (such as interleukins-1beta and 6 and tumor necrosis factor-alpha) have been further detailed, and new early mediators (e.g., complement factor 5a and platelet-activating factor) have been proposed. Our understanding of how peripheral inflammatory messengers cross the blood-brain barrier (BBB) has changed. The view that the organum vasculosum of the lamina terminalis is the major port of entry for pyrogenic cytokines has lost its dominant position. The vagal theory has emerged and then fallen. Consensus has been reached that the BBB is not a divider preventing signal transduction, but rather the transducer itself. In the endothelial and perivascular cells of the BBB, upstream signaling molecules (e.g., pro-inflammatory cytokines) are switched to a downstream mediator, prostaglandin (PG) E2. An indispensable role of PGE2 in the febrile response to LPS has been demonstrated in studies with targeted disruption of genes encoding either PGE2-synthesizing enzymes or PGE2 receptors. The PGE2-synthesizing enzymes include numerous phospholipases (PL) A2, cyclooxygenases (COX)-1 and 2, and several newly discovered terminal PGE synthases (PGES). It has been realized that the

  6. Therapeutic Hypothermia for Cardioprotection in Acute Myocardial Infarction

    PubMed Central

    Kang, In Sook; Fumiaki, Ikeno

    2016-01-01

    Mild therapeutic hypothermia of 32–35℃ improved neurologic outcomes in outside hospital cardiac arrest survivor. Furthermore, in experimental studies on infarcted model and pilot studies on conscious patients with acute myocardial infarction, therapeutic hypothermia successfully reduced infarct size and microvascular resistance. Therefore, mild therapeutic hypothermia has received an attention as a promising solution for reduction of infarction size after acute myocardial infarction which are not completely solved despite of optimal reperfusion therapy. Nevertheless, the results from randomized clinical trials failed to prove the cardioprotective effects of therapeutic hypothermia or showed beneficial effects only in limited subgroups. In this article, we reviewed rationale for therapeutic hypothermia and possible mechanisms from previous studies, effective methods for clinical application to the patients with acute myocardial infarction, lessons from current clinical trials and future directions. PMID:26847278

  7. Therapeutic hypothermia after cardiac arrest: outcome predictors

    PubMed Central

    Leão, Rodrigo Nazário; Ávila, Paulo; Cavaco, Raquel; Germano, Nuno; Bento, Luís

    2015-01-01

    Objective The determination of coma patient prognosis after cardiac arrest has clinical, ethical and social implications. Neurological examination, imaging and biochemical markers are helpful tools accepted as reliable in predicting recovery. With the advent of therapeutic hypothermia, these data need to be reconfirmed. In this study, we attempted to determine the validity of different markers, which can be used in the detection of patients with poor prognosis under hypothermia. Methods Data from adult patients admitted to our intensive care unit for a hypothermia protocol after cardiac arrest were recorded prospectively to generate a descriptive and analytical study analyzing the relationship between clinical, neurophysiological, imaging and biochemical parameters with 6-month outcomes defined according to the Cerebral Performance Categories scale (good 1-2, poor 3-5). Neuron-specific enolase was collected at 72 hours. Imaging and neurophysiologic exams were carried out in the 24 hours after the rewarming period. Results Sixty-seven patients were included in the study, of which 12 had good neurological outcomes. Ventricular fibrillation and electroencephalographic theta activity were associated with increased likelihood of survival and improved neurological outcomes. Patients who had more rapid cooling (mean time of 163 versus 312 minutes), hypoxic-ischemic brain injury on magnetic resonance imaging or neuron-specific enolase > 58ng/mL had poor neurological outcomes (p < 0.05). Conclusion Hypoxic-ischemic brain injury on magnetic resonance imaging and neuron-specific enolase were strong predictors of poor neurological outcomes. Although there is the belief that early achievement of target temperature improves neurological prognoses, in our study, there were increased mortality and worse neurological outcomes with earlier target-temperature achievement. PMID:26761469

  8. [Pathophysiology and management of perioperative hypothermia].

    PubMed

    Witkowski, Wojciech; Maj, Jakub

    2006-06-01

    The paper is a review of pathophysiology and management of perioperative hypothermia. The advanced methods of rewarming, such as passive and active: external and core used in clinic allow for efficient management ant prophylactics of hypothermia. Thermotherapy with use of infrared ceiling heaters CTS and mobile MTC as well as Infutherm system applying by authors are desirable and even indispensable in contemporary equipment of surgery clinics, cardiovascular surgery clinics and burn centers. The ideal rewarming method should be safe and enable fast, reliable and predictable warming or rewarming. The clinical parameter to determine the efficacy of rewarming is the change of core temperature. There is no doubt that active warming with forced-air warmers (Warm Touch 5700 and Bair Hugger 500) or radiative heaters (IR-A:Hydrosun 500, IR-C radiation: CTC X, MTC) is more effective than use of standard, passive insulation hospital blankets or convectional heaters. Actually the forced-air warmers are counted to be more useful in cardiovascular surgery hypothermia management, because of fast rate core temperature rise and faster rise in mean skin temperature compared to the control group. CTC X and MTC Aragona radiative heaters are useful in burn management being the most effective when the distance of heater from the patient body is less than 80 cm. The observation of 60 consecutive extensive burns leads to conclusion that long-lasting dressings in burn patients when the whole body is not covered and protected, can be performed safely only in conditions excluding heat losses and core temperature drop. While the cold intravenous fluids may significantly contribute to the temperature drop depending on the volume infused, the use of fluids warming systems as well as external heat application is absolutely indicated to improve the heat balance of the patient body. PMID:17007255

  9. Hypothermia attenuates apoptosis and protects contact between myelin basic protein-expressing oligodendroglial-lineage cells and neurons against hypoxia-ischemia.

    PubMed

    Ichinose, Mari; Kamei, Yoshimasa; Iriyama, Takayuki; Imada, Shinya; Seyama, Takahiro; Toshimitsu, Masatake; Asou, Hiroaki; Yamamoto, Masahiro; Fujii, Tomoyuki

    2014-10-01

    Periventricular leukomalacia (PVL) is a major form of brain injury among preterm infants, which is characterized by extensive loss and dysfunction of premyelinating oligodendrocytes (pre-OLs) induced by hypoxia-ischemia (HI). Therapeutic hypothermia, which is a standard treatment for term infants with HI encephalopathy, is not indicated for preterm infants because its safety and effect have not been established. Here we investigate the effectiveness and mechanism of hypothermia for the inhibition of pre-OLs damage in PVL. For in vivo studies, 6-day-old rats underwent left carotid artery ligation, followed by exposure to 6% oxygen for 1 hr under hypothermic or normothermic conditions. The loss of myelin basic protein (MBP) was inhibited by hypothermia. For in vitro studies, primary pre-OLs cultures were subjected to oxygen-glucose deprivation (OGD) under normothermic or hypothermic conditions, and dorsal root ganglion neurons were subsequently added. Hypothermia inhibited apoptosis of pre-OLs, and, despite specific downregulation of 21.5- and 17-kDa MBP mRNA expression during hypothermia, recovery of the expression after OGD was superior compared with normothermia. OGD caused disarrangement of MBP distribution, decreased the levels of phosphorylated 21.5-kDa MBP, and disturbed the capacity to contact with neurons, all of which were restored by hypothermia. Pharmacological inhibition of ERK1/2 phosphorylation with U0126 during and after OGD significantly reduced the protective effects of hypothermia on apoptosis and myelination, respectively. These data suggest that phosphorylated exon 2-containing (21.5- and possibly 17-kDa) MBP isoforms may play critical roles in myelination and that hypothermia attenuates apoptosis and preserves the contact between OLs and neurons via ERK1/2 phosphorylation. PMID:24865975

  10. Optimization of induction of mild therapeutic hypothermia with cold saline infusion: A laboratory experiment.

    PubMed

    Fluher, Jure; Markota, Andrej; Stožer, Andraž; Sinkovič, Andreja

    2015-01-01

    Cold fluid infusions can be used to induce mild therapeutic hypothermia after cardiac arrest. Fluid temperature higher than 4°C can increase the volume of fluid needed, prolong the induction phase of hypothermia and thus contribute to complications. We performed a laboratory experiment with two objectives. The first objective was to analyze the effect of wrapping fluid bags in ice packs on the increase of fluid temperature with time in bags exposed to ambient conditions. The second objective was to quantify the effect of insulating venous tubing and adjusting flow rate on fluid temperature increase from bag to the level of an intravenous cannula during a simulated infusion. The temperature of fluid in bags wrapped in ice packs was significantly lower compared to controls at all time points during the 120 minutes observation. The temperature increase from the bag to the level of intravenous cannula was significantly lower for insulated tubing at all infusion rates (median temperature differences between bag and intravenous cannula were: 8.9, 4.8, 4.0, and 3.1°C, for non-insulated and 5.9, 3.05, 1.1, and 0.3°C, for insulated tubing, at infusion rates 10, 30, 60, and 100 mL/minute, respectively). The results from this study could potentially be used to decrease the volume of fluid infused when inducing mild hypothermia with an infusion of cold fluids. PMID:26614854

  11. Serotonin and Dopamine Protect from Hypothermia/Rewarming Damage through the CBS/ H2S Pathway

    PubMed Central

    Talaei, Fatemeh; Bouma, Hjalmar R.; Van der Graaf, Adrianus C.; Strijkstra, Arjen M.; Schmidt, Martina; Henning, Robert H.

    2011-01-01

    Biogenic amines have been demonstrated to protect cells from apoptotic cell death. Herein we show for the first time that serotonin and dopamine increase H2S production by the endogenous enzyme cystathionine-β-synthase (CBS) and protect cells against hypothermia/rewarming induced reactive oxygen species (ROS) formation and apoptosis. Treatment with both compounds doubled CBS expression through mammalian target of rapamycin (mTOR) and increased H2S production in cultured rat smooth muscle cells. In addition, serotonin and dopamine treatment significantly reduced ROS formation. The beneficial effect of both compounds was minimized by inhibition of their re-uptake and by pharmacological inhibition of CBS or its down-regulation by siRNA. Exogenous administration of H2S and activation of CBS by Prydoxal 5′-phosphate also protected cells from hypothermic damage. Finally, serotonin and dopamine pretreatment of rat lung, kidney, liver and heart prior to 24 h of hypothermia at 3°C followed by 30 min of rewarming at 37°C upregulated the expression of CBS, strongly reduced caspase activity and maintained the physiological pH compared to untreated tissues. Thus, dopamine and serotonin protect cells against hypothermia/rewarming induced damage by increasing H2S production mediated through CBS. Our data identify a novel molecular link between biogenic amines and the H2S pathway, which may profoundly affect our understanding of the biological effects of monoamine neurotransmitters. PMID:21829469

  12. Short- and long-latency somatosensory neuronal responses reveal selective brain injury and effect of hypothermia in global hypoxic ischemia

    PubMed Central

    Wu, Dan; Xiong, Wei; Jia, Xiaofeng; Geocadin, Romergryko G.

    2012-01-01

    Evoked potentials recorded from the somatosensory cortex have been shown to be an electrophysiological marker of brain injury in global hypoxic ischemia (HI). The evoked responses in somatosensory neurons carry information pertaining to signal from the ascending pathway in both the subcortical and cortical areas. In this study, origins of the subcortical and cortical signals are explored by decomposing the evoked neuronal activities into short- and long-latency responses (SLR and LLR), respectively. We evaluated the effect of therapeutic hypothermia on SLR and LLR during early recovery from cardiac arrest (CA)-induced HI in a rodent model. Twelve rats were subjected to CA, after which half of them were treated with hypothermia (32–34°C) and the rest were kept at normal temperature (36–37°C). Evoked neuronal activities from the primary somatosensory cortex, including multiunit activity (MUA) and local field potential (LFP), were continuously recorded during injury and early recovery. Results showed that upon initiation of injury, LLR disappeared first, followed by the disappearance of SLR, and after a period of isoelectric silence SLR reappeared prior to LLR. This suggests that cortical activity, which primarily underlies the LLR, may be more vulnerable to ischemic injury than SLR, which relates to subcortical activity. Hypothermia potentiated the SLR but suppressed the LLR by delaying its recovery after CA (hypothermia: 38.83 ± 5.86 min, normothermia: 23.33 ± 1.15 min; P < 0.05) and attenuating its amplitude, suggesting that hypothermia may selectively downregulate cortical activity as an approach to preserve the cerebral cortex. In summary, our study reveals the vulnerability of the somatosensory neural structures to global HI and the differential effects of hypothermia on these structures. PMID:22157111

  13. The therapeutic potential of regulated hypothermia.

    PubMed

    Gordon, C J

    2001-03-01

    Reducing body temperature of rodents has been found to improve their survival to ischaemia, hypoxia, chemical toxicants, and many other types of insults. Larger species, including humans, may also benefit from a lower body temperature when recovering from CNS ischaemia and other traumatic insults. Rodents subjected to these insults undergo a regulated hypothermic response (that is, decrease in set point temperature) characterised by preference for cooler ambient temperatures, peripheral vasodilatation, and reduced metabolic rate. However, forced hypothermia (that is, body temperature forced below set point) is the only method used in the study and treatment of human pathological insults. The therapeutic efficacy of the hypothermic treatment is likely to be influenced by the nature of the reduction in body temperature (that is, forced versus regulated). Homeostatic mechanisms counter forced reductions in body temperature resulting in physiological stress and decreased efficacy of the hypothermic treatment. On the other hand, regulated hypothermia would seem to be the best means of achieving a therapeutic benefit because thermal homeostatic systems mediate a controlled reduction in core temperature. PMID:11300205

  14. Hypothermia during Carotid Endarterectomy: A Safety Study

    PubMed Central

    Candela, Serena; Dito, Raffaele; Casolla, Barbara; Silvestri, Emanuele; Sette, Giuliano; Filippi, Federico; Taurino, Maurizio; Brancadoro, Domitilla; Orzi, Francesco

    2016-01-01

    Background CEA is associated with peri-operative risk of brain ischemia, due both to emboli production caused by manipulation of the plaque and to potentially noxious reduction of cerebral blood flow by carotid clamping. Mild hypothermia (34–35°C) is probably the most effective approach to protect brain from ischemic insult. It is therefore a substantial hypothesis that hypothermia lowers the risk of ischemic brain damage potentially associated with CEA. Purpose of the study is to test whether systemic endovascular cooling to a target of 34.5–35°C, initiated before and maintained during CEA, is feasible and safe. Methods The study was carried out in 7 consecutive patients referred to the Vascular Surgery Unit and judged eligible for CEA. Cooling was initiated 60–90 min before CEA, by endovascular approach (Zoll system). The target temperature was maintained during CEA, followed by passive, controlled rewarming (0.4°C/h). The whole procedure was carried out under anesthesia. Results All the patients enrolled had no adverse events. Two patients exhibited a transient bradycardia (heart rate 30 beats/min). There were no significant differences in the clinical status, laboratory and physiological data measured before and after CEA. Conclusions Systemic cooling to 34.5–35.0°C, initiated before and maintained during carotid clamping, is feasible and safe. Trial Registration ClinicalTrials.gov NCT02629653 PMID:27058874

  15. The Effect of Hypothermia on the Expression of TIMP-3 after Traumatic Brain Injury in Rats

    PubMed Central

    Jia, Feng; Mao, Qing; Liang, Yu-min

    2014-01-01

    Abstract Here we investigate the effect of hypothermia on the expression of apoptosis-regulating protein TIMP-3 after fluid percussion traumatic brain injury (TBI) in rats. We began with 210 adult male Sprague-Dawley rats and randomly assigned them to three groups: TBI with hypothermia treatment (32°C), TBI with normothermia (37°C), and sham-injured controls. TBI was induced by a fluid percussion TBI device. Mild hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 h. The rats were killed at 4, 6, 12, 24, 48, and 72 h and 1 week after TBI. The mRNA and protein level of TIMP-3 in both the injured and uninjured hemispheres of the brains from each group were measured using RT-PCR and Western blotting. In the normothermic group, TIMP-3 levels in both the injured and uninjured hemispheres were significantly increased after TBI compared with those of sham-injured animals (p < 0.01). In contrast, post-traumatic hypothermia significantly attenuated this increase. According to the RT-PCR and Western blot analyses, the maximum mRNA levels of TIMP-3 were reduced to 60.60 ± 2.30%, 55.83 ± 1.80%, 66.03 ± 2.10%, and 64.51 ± 1.50%, respectively, of the corresponding values in the normothermic group in the injured and uninjured hemispheres (cortex and hippocampus) of the hypothermia group (p < 0.01), while the respective maximum protein levels of TIMP-3 were reduced to 57.50 ± 1.50, 52.67 ± 2.20, 60.31 ± 2.50 and 54.76 ± 1.40 (p < 0.01). Our data suggest that moderate fluid percussion brain injury significantly upregulates TIMP-3 expression, and that this increase may be suppressed by hypothermia treatment. PMID:23256480

  16. Rapid induction of therapeutic hypothermia using convective-immersion surface cooling: Safety, efficacy and outcomes☆

    PubMed Central

    Howes, Daniel; Ohley, William; Dorian, Paul; Klock, Cathy; Freedman, Robert; Schock, Robert; Krizanac, Danica; Holzer, Michael

    2010-01-01

    Therapeutic hypothermia has become an accepted part of post-resuscitation care. Efforts to shorten the time from return of spontaneous circulation to target temperature have led to the exploration of different cooling techniques. Convective-immersion uses a continuous shower of 2°C water to rapidly induce hypothermia. The primary purpose of this multi-center trial was to evaluate the feasibility and speed of convective-immersion cooling in the clinical environment. The secondary goal was to examine the impact of rapid hypothermia induction on patient outcome. 24 post-cardiac arrest patients from 3 centers were enrolled in the study; 22 agreed to participate until the 6-month evaluations were completed. The median rate of cooling was 3.0°C/h. Cooling times were shorter than reported in previous studies. The median time to cool the patients to target temperature (<34°C) was 37 min (range 14–81 min); and only 27 min in a subset of patients sedated with propofol. Survival was excellent, with 68% surviving to 6 months; 87% of survivors were living independently at 6 months. Conductive-immersion surface cooling using the ThermoSuit® System is a rapid, effective method of inducing therapeutic hypothermia. Although the study was not designed to demonstrate impact on outcomes, survival and neurologic function were superior to those previously reported, suggesting comparative studies should be undertaken. Shortening the delay from return of spontaneous circulation to hypothermic target temperature may significantly improve survival and neurologic outcome and warrants further study. PMID:20122778

  17. Intra-arrest hypothermia during cardiac arrest: a systematic review

    PubMed Central

    2012-01-01

    Introduction Therapeutic hypothermia is largely used to protect the brain following return of spontaneous circulation (ROSC) after cardiac arrest (CA), but it is unclear whether we should start therapeutic hypothermia earlier, that is, before ROSC. Methods We performed a systematic search of PubMed, EMBASE, CINAHL, the Cochrane Library and Ovid/Medline databases using "arrest" OR "cardiac arrest" OR "heart arrest" AND "hypothermia" OR "therapeutic hypothermia" OR "cooling" as keywords. Only studies using intra-arrest therapeutic hypothermia (IATH) were selected for this review. Three authors independently assessed the validity of included studies and extracted data regarding characteristics of the studied cohort (animal or human) and the main outcomes related to the use of IATH: Mortality, neurological status and cardiac function (particularly, rate of ROSC). Results A total of 23 animal studies (level of evidence (LOE) 5) and five human studies, including one randomized controlled trial (LOE 1), one retrospective and one prospective controlled study (LOE 3), and two prospective studies without a control group (LOE 4), were identified. IATH improved survival and neurological outcomes when compared to normothermia and/or hypothermia after ROSC. IATH was also associated with improved ROSC rates and with improved cardiac function, including better left ventricular function, and reduced myocardial infarct size, when compared to normothermia. Conclusions IATH improves survival and neurological outcome when compared to normothermia and/or conventional hypothermia in experimental models of CA. Clinical data on the efficacy of IATH remain limited. PMID:22397519

  18. Preventing admission hypothermia in very low birth weight neonates.

    PubMed

    Fawcett, Kristin

    2014-01-01

    Neonatal hypothermia, temperature < 36.5°C, is a major contributor to neonatal mortality and morbidity. hypothermia of preterm infants remains a challenge in the NiCU for many reasons. preterm very low birth weight (VlBW) infants, those infants born <1,500 g, are prone to very rapid heat losses through mechanisms of convection, evaporation, conduction, and radiation. this article reviews current research to reduce and prevent mortality and morbidity from hypothermia in preterm VlBW infants by implementing interventions in the delivery room to minimize heat loss and maintain core body temperatures. PMID:24816875

  19. Mechanisms responsible for decreased glomerular filtration in hibernation and hypothermia

    NASA Technical Reports Server (NTRS)

    Tempel, G. E.; Musacchia, X. J.; Jones, S. B.

    1977-01-01

    Measurements of blood pressure, heart rate, red blood cell and plasma volumes, and relative distribution of cardiac output were made on hibernating and hypothermic adult male and female golden hamsters weighing 120-140 g to study the mechanisms underlying the elimination or marked depression of renal function in hibernation and hypothermia. The results suggest that the elimination or marked depression in renal function reported in hibernation and hypothermia may partly be explained by alterations in cardiovascular system function. Renal perfusion pressure which decreases nearly 60% in both hibernation and hypothermia and a decrease in plasma volume of roughly 35% in the hypothermic animal might both be expected to markedly alter glomerular function.

  20. Short Duration Combined Mild Hypothermia Improves Resuscitation Outcomes in a Porcine Model of Prolonged Cardiac Arrest

    PubMed Central

    Yu, Tao; Yang, Zhengfei; Li, Heng; Ding, Youde; Huang, Zitong; Li, Yongqin

    2015-01-01

    Objective. In this study, our aim was to investigate the effects of combined hypothermia with short duration maintenance on the resuscitation outcomes in a porcine model of ventricular fibrillation (VF). Methods. Fourteen porcine models were electrically induced with VF and untreated for 11 mins. All animals were successfully resuscitated manually and then randomized into two groups: combined mild hypothermia (CH group) and normothermia group (NT group). A combined hypothermia of ice cold saline infusion and surface cooling was implemented in the animals of the CH group and maintained for 4 hours. The survival outcomes and neurological function were evaluated every 24 hours until a maximum of 96 hours. Neuron apoptosis in hippocampus was analyzed. Results. There were no significant differences in baseline physiologies and primary resuscitation outcomes between both groups. Obvious improvements of cardiac output were observed in the CH group at 120, 180, and 240 mins following resuscitation. The animals demonstrated better survival at 96 hours in the CH group when compared to the NT group. In comparison with the NT group, favorable neurological functions were observed in the CH group. Conclusion. Short duration combined cooling initiated after resuscitation improves survival and neurological outcomes in a porcine model of prolonged VF. PMID:26558261

  1. Mild hypothermia during advanced life support: a preliminary study in out-of-hospital cardiac arrest

    PubMed Central

    Bruel, Cédric; Parienti, Jean-Jacques; Marie, William; Arrot, Xavier; Daubin, Cédric; Du Cheyron, Damien; Massetti, Massimo; Charbonneau, Pierre

    2008-01-01

    Introduction Induction of mild hypothermia after cardiac arrest may confer neuroprotection. We assessed the feasibility, safety and effectiveness of therapeutic infusion of 2 l of normal saline at 4°C before return of spontaneous circulation during cardiopulmonary resuscitation after out of hospital cardiac arrest. Methods This was a prospective, observational, multicenter clinical trial conducted in Emergency Medical Services units and in a medical intensive care unit at Caen University Hospital, Cen, France. Results In patients who had suffered out of hospital cardiac arrest, hypothermia was induced by infusing 2 l of 4°C NaCl 0.9% over 30 minutes during advanced life support prior to arrival at the hospital. A total of 33 patients were included in the study. Eight patients presented with ventricular fibrillation as the initial cardiac rhythm. Mild hypothermia was achieved after a median of 16 minutes (interquartile range 11.5 to 25.0 minutes) after return of spontaneous circulation. After intravenous cooling, the temperature decreased by 2.1°C (P < 0.0001) to a mean body temperature of 33.3°C (interquartile range 32.3 to 34.3°C). The only observed adverse event was pulmonary oedema, which occurred in one patient. Conclusion We concluded that prehospital induction of therapeutic hypothermia using infusion of 2 l of 4°C normal saline during advanced life support was feasible, effective and safe. Larger studies are required to assess the impact that this early cooling has on neurological outcomes after cardiac arrest. PMID:18312676

  2. Neuroprotection and hypothermia in infants and children.

    PubMed

    Pietrini, Domenico; Piastra, Marco; Luca, Ersilia; Mancino, Aaldo; Conti, Giorgio; Cavaliere, Franco; De Luca, Daniele

    2012-06-01

    Brain injury is the leading cause of death in pediatric ICU. Current evidence supports the use of therapeutic hypothermia (TH) in unconscious patients after out-of-hospital cardiac arrest when the initial heart rhythm was ventricular fibrillation. TH has been proved to be also beneficial in term neonates after hypoxic-ischemic encephalopathy (HIE) and in children with traumatic brain injury (TBI). Recent reports have also investigated TH for the treatment of superrefractory status epilepticus. The clinical application of TH is based on the possibility to inhibit or lessen a myriad of destructive processes (including excitotoxicty, neuroinflammation, apoptosis, free radical production, seizure activity, blood- brain barrier disruption, blood vessel leakage) that take place in the injured tissue following ischemia-reperfusion. TH may also represent a useful tool when conventional therapy fails to achieve an effective control of elevated intracranial pressure. This review is aimed to provide an update of the available literature concerning this intriguing topic. PMID:22512392

  3. Therapeutic Hypothermia for Neonatal Encephalopathy and Extracorporeal Membrane Oxygenation

    PubMed Central

    Massaro, An; Rais-Bahrami, Khodayar; Chang, Taeun; Glass, Penny; Short, Billie Lou; Baumgart, Stephen

    2010-01-01

    This case series describes clinical management of five infants who received whole-body cooling during extracorporeal membrane oxygenation (ECMO). We maintained systemic hypothermia during ECMO with acceptable clinical outcomes. PMID:20472254

  4. A team approach to the prevention of unplanned postoperative hypothermia.

    PubMed

    Bitner, Jason; Hilde, Leana; Hall, Kenneth; Duvendack, Tammy

    2007-05-01

    Postoperative hypothermia (ie, a core temperature lower than 96.8 degrees F [36 degrees C]), is a problem frequently seen in surgical patients, especially those undergoing total joint replacement. Patients who experience hypothermia may have increased recovery times and postoperative complications. A team of clinical staff members and personnel from the performance improvement (PI) department of a hospital used a PI model to incorporate use of preoperative forced-air warming blankets that resulted in improved postoperative core temperatures. PMID:17499055

  5. Therapeutic hypothermia attenuates tissue damage and cytokine expression after traumatic brain injury by inhibiting necroptosis in the rat

    PubMed Central

    Liu, Tao; Zhao, Dong-xu; Cui, Hua; Chen, Lei; Bao, Ying-hui; Wang, Yong; Jiang, Ji-yao

    2016-01-01

    Necroptosis has been shown as an alternative form of cell death in many diseases, but the detailed mechanisms of the neuron loss after traumatic brain injury (TBI) in rodents remain unclear. To investigate whether necroptosis is induced after TBI and gets involved in the neuroprotecton of therapeutic hypothermia on the TBI, we observed the pathological and biochemical change of the necroptosis in the fluid percussion brain injury (FPI) model of the rats. We found that receptor-interacting protein (RIP) 1 and 3, and mixed lineage kinase domain-like protein (MLKL), the critical downstream mediators of necroptosis recently identified in vivo, as well as HMGB1 and the pro-inflammation cytokines TNF-α, IL-6 and IL-18, were increased at an early phase (6 h) in cortex after TBI. Posttraumatic hypothermia (33 °C) led to the decreases in the necroptosis regulators, inflammatory factors and brain tissue damage in rats compared with normothermia-treated TBI animals. Immunohistochemistry studies showed that posttraumatic hypothermia also decreased the necroptosis-associated proteins staining in injured cortex and hippocampal CA1. Therefore, we conclude that the RIP1/RIP3-MLKL-mediated necroptosis occurs after experimental TBI and therapeutic hypothermia may protect the injured central nervous system from tissue damage and the inflammatory responses by targeting the necroptosis signaling after TBI. PMID:27080932

  6. The transcriptome responses of cardiomyocyte exposed to hypothermia.

    PubMed

    Zhang, Jian; Xue, Xiaodong; Xu, Yinli; Zhang, Yuji; Li, Zhi; Wang, Huishan

    2016-06-01

    Hypothermia has positive and negative consequences on the body. Hypothermia depresses myocardial contraction, conduction, and metabolic rate in the heart. However, little is known about the underlying molecular mechanisms. Herein, we compared the gene expression of human adult ventricular cardiomyocytes (AC16) under hypothermia to find differences between different temperatures, and elucidate the candidate genes that may play important roles in the response to hypothermia. A total of 2413 differentially expressed genes (DEGs) were identified by microarray hybridization, which provided abundant data for further analysis. Gene Ontology (GO) enrichment analysis revealed that genes related to transcription, and protein and lipid metabolism were significantly enriched. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that DEGs were significantly enriched in TGF-β pathway and cytokine-cytokine receptor interaction, which may play important roles in changes affected by hypothermia. A set of transcription factors (TFs) (CPBP, Churchill, NF-AT1, GKLF, SRY, ZNF333, ING4, myogenin, DRI1 and CRX) was recognized to be the functional layer of key nodes, which mapped the signal of hypothermia to transcriptome. The identified DEGs, pathways and predicted TFs could facilitate further investigations of the detailed molecular mechanisms. PMID:27039159

  7. Hypothermia associated with clobazam use in adult epilepsy.

    PubMed

    Gauthier, Angela C; Quraishi, Imran H; Mattson, Richard H

    2016-01-01

    Clobazam, a 1,5-benzodiazepine FDA-approved in 2011, is commonly used to treat anxiety and epilepsy. It has not associated with hypothermia until very recently, in a case report involving two pediatric patients. Here, we report the first case of hypothermia development in an adult patient with epilepsy associated with clobazam use. A couple months after starting clobazam, the patient started developing episodes of hypothermia every several weeks, with temperatures ranging from 90 °F-95 °F. Normothermia was achieved with Bair Hugger therapy. Thyroid-stimulating hormone and cortisol levels were normal, and there was no evidence of infection in most instances. After 11 total episodes of hypothermia over a year of clobazam use, the drug was discontinued. It has now been 7 months after discontinuation, and the patient has not experienced any more episodes of hypothermia. Early recognition of the link between clobazam and hypothermia may prevent avoidable Emergency Department visits and hospitalizations. PMID:26870662

  8. Successful Use of Therapeutic Hypothermia in a Pregnant Patient.

    PubMed

    Oguayo, Kevin N; Oyetayo, Ola O; Stewart, David; Costa, Steven M; Jones, Richard O

    2015-08-01

    Out-of-hospital cardiac arrest is a leading cause of death in the United States. Pregnant women are not immune to cardiac arrest, and the treatment of such patients can be difficult. Pregnancy is a relative contraindication to the use of therapeutic hypothermia after cardiac arrest. A 20-year-old woman who was 18 weeks pregnant had an out-of-hospital cardiac arrest. Upon her arrival at the emergency department, she was resuscitated and her circulation returned spontaneously, but her score on the Glasgow Coma Scale was 3. After adequate family discussion of the risks and benefits of therapeutic hypothermia, a decision was made to initiate therapeutic hypothermia per established protocol for 24 hours. The patient was successfully cooled and rewarmed. By the time she was discharged, she had experienced complete neurologic recovery, apart from some short-term memory loss. Subsequently, at 40 weeks, she delivered vaginally a 7-lb 3-oz girl whose Apgar scores were 8 and 9, at 1 and 5 minutes respectively. To our knowledge, this is only the 3rd reported case of a successful outcome following the initiation of therapeutic hypothermia for out-of-hospital cardiac arrest in a pregnant woman. On the basis of this and previous reports of successful outcomes, we recommend that therapeutic hypothermia be considered an option in the management of out-of-hospital cardiac arrest in the pregnant population. To facilitate a successful outcome, a multidisciplinary approach involving cardiology, emergency medicine, obstetrics, and neurology should be used. PMID:26413021

  9. Association between thymoma and persistent hypothermia: a case report

    PubMed Central

    2009-01-01

    Introduction Thymomas are rare, slow-growing tumours that present in a variety of ways such as incidental findings on chest radiographs following symptoms of cough and dyspnoea. Thymomas may also present with symptoms due to intrathoracic spread such as superior vena cava obstruction, or with symptoms of an associated paraneoplastic disorder. Such paraneoplastic disorders are typified by the generation of autoantibodies directed against a variety of self antigens including myasthenia gravis, neuromyotonia, and hypogammaglobulinaemia. Significant hypothermia in association with thymoma has been described previously in one published case report. The basis for hypothermia in that case was not clear, but was postulated to relate to abnormal central thermal regulation and was resolved completely following treatment with intravenous gammablobulin, thus suggesting an autoimmune aetiology. Case presentation We present the case of an 88-year-old man with Type A thymoma and persistent hypothermia. An extensive investigation of the hypothermia revealed no aetiology other than the thymoma itself. Symptoms of hypothermia were treated effectively with passive and active external rewarming. The patient's dyspnoea was much improved by intercostal drainage of a left-sided pleural effusion and talc pleurodesis. He was not offered definitive treatment for the thymoma in view of its relatively favourable prognosis, and because his symptoms were well controlled at the time of discharge. Conclusion We suggest that the possibility of thymoma be investigated once the more common causes of hypothermia have been excluded in an appropriate clinical context. To the best of our knowledge, this is only the second published case report describing such an association. PMID:19946549

  10. Short- and Long-Term Outcomes in Very Low Birth Weight Infants with Admission Hypothermia

    PubMed Central

    Wang, Shwu-Meei; Lung, Hou-Ling; Chang, Jui-Hsing; Hsu, Chyong-Hsin; Jim, Wai-Tim; Lee, Ching-Hsiao; Hung, Hsiao-Fang

    2015-01-01

    Background Neonatal hypothermia remains a common problem and is related to elevated morbidities and mortality. However, the long-term neurodevelopmental effects of admission hypothermia are still unknown. This study attempted to determine the short-term and long-term consequences of admission hypothermia in VLBW preterm infants. Study Design This retrospective study measured the incidence and compared the outcomes of admission hypothermia in very low birth weight (VLBW) preterm infants in a tertiary-level neonatal intensive care unit. Infants were divided into the following groups: normothermia (36.5–37.5°C), mild hypothermia (36.0–36.4°C), moderate hypothermia (32.0–35.9°C), and severe hypothermia (< 32°C). We compared the distribution, demographic variables, short-term outcomes, and neurodevelopmental outcomes at 24 months of corrected age among groups. Results We studied 341 infants: 79 with normothermia, 100 with mild hypothermia, 162 with moderate hypothermia, and 0 with severe hypothermia. Patients in the moderate hypothermia group had significantly lower gestational ages (28.1 wk vs. 29.7 wk, P < .02) and smaller birth weight (1004 g vs. 1187 g, P < .001) compared to patients in the normothermia group. Compared to normothermic infants, moderately hypothermic infants had significantly higher incidences of 1-min Apgar score < 7 (63.6% vs. 31.6%, P < .001), respiratory distress syndrome (RDS) (58.0% vs. 39.2%, P = .006), and mortality (18.5% vs. 5.1%, P = .005). Moderate hypothermia did not affect neurodevelopmental outcomes at 2 years’ corrected age. Mild hypothermia had no effect on short-term or long-term outcomes. Conclusions Admission hypothermia was common in VLBW infants and correlated inversely with birth weight and gestational age. Although moderate hypothermia was associated with higher RDS and mortality rates, it may play a limited role among multifactorial causes of neurodevelopmental impairment. PMID:26193370

  11. Hypothermia as a cause of coagulopathy during hepatectomy.

    PubMed

    Lau, Albert Wai-Cheung; Chen, Chia-Chen; Wu, Rick Sai-Chuen; Poon, Kin-Shing

    2010-06-01

    We report a 27-year-old hemostatically competent female scheduled for partial hepatectomy. During the operation, she experienced an accidental inferior vena cava tear and suffered acute blood loss. After fluid resuscitation and blood transfusion, she developed hypothermia, with a temperature of 33.8 degrees C, and severe coagulopathy with activated clotting time exceeding 1500 seconds measured using the Hemochron Response system (ITC, Edison, NJ, USA). Despite sufficient blood transfusion and correction of her electrolyte imbalance, the poor hemostasis persisted. After per-forming peritoneal lavage with warm saline, her condition dramatically improved and her hypothermia and severe coagulopathy were reversed. PMID:20643371

  12. Therapeutic hypothermia and targeted temperature management in traumatic brain injury: Clinical challenges for successful translation.

    PubMed

    Dietrich, W Dalton; Bramlett, Helen M

    2016-06-01

    The use of therapeutic hypothermia (TH) and targeted temperature management (TTM) for severe traumatic brain injury (TBI) has been tested in a variety of preclinical and clinical situations. Early preclinical studies showed that mild reductions in brain temperature after moderate to severe TBI improved histopathological outcomes and reduced neurological deficits. Investigative studies have also reported that reductions in post-traumatic temperature attenuated multiple secondary injury mechanisms including excitotoxicity, free radical generation, apoptotic cell death, and inflammation. In addition, while elevations in post-traumatic temperature heightened secondary injury mechanisms, the successful implementation of TTM strategies in injured patients to reduce fever burden appear to be beneficial. While TH has been successfully tested in a number of single institutional clinical TBI studies, larger randomized multicenter trials have failed to demonstrate the benefits of therapeutic hypothermia. The use of TH and TTM for treating TBI continues to evolve and a number of factors including patient selection and the timing of the TH appear to be critical in successful trial design. Based on available data, it is apparent that TH and TTM strategies for treating severely injured patients is an important therapeutic consideration that requires more basic and clinical research. Current research involves the evaluation of alternative cooling strategies including pharmacologically-induced hypothermia and the combination of TH or TTM approaches with more selective neuroprotective or reparative treatments. This manuscript summarizes the preclinical and clinical literature emphasizing the importance of brain temperature in modifying secondary injury mechanisms and in improving traumatic outcomes in severely injured patients. This article is part of a Special Issue entitled SI:Brain injury and recovery. PMID:26746342

  13. Microdialysis as Clinical Evaluation of Therapeutic Hypothermia in Rat Subdural Hematoma Model.

    PubMed

    Yokobori, Shoji; Spurlock, Markus S; Lee, Stephanie W; Gajavelli, Shyam; Bullock, Ross M

    2016-01-01

    Cerebral microdialysis (MD) is a fine laboratory technique which has been established for studying physiological, pharmacological, and pathological changes in the experimental studies of traumatic brain injury (TBI). This technique has also been well translated and widely applied to clinical bedside monitoring to provide pathophysiological analysis in severe TBI patients. The MD technique is thus well suited for straightforward translation from basic science to clinical application.In this chapter, we describe our evaluation of MD method in acute subdural hematoma (ASDH) rat model. With 100 kDa cut-off microdialysis membrane, we could measure several biomarkers such as ubiquitin carboxy hydrolase L1 (UCH-L1), a neuronal marker and glial fibrillary acidic protein (GFAP), and a glial marker in extracellular fluid. In this experiment, we could detect that the peak of extracellular UCH-L1 in the early hypothermia group was significantly lower than in the normothermia group. Also, in the late phase of reperfusion (>2.5 h after decompression), extracellular GFAP in the early hypothermia group was lower than in the normothermia. These data thus suggested that early, preoperatively induced hypothermia could mediate the reduction of neuronal and glial damage in the reperfusion phase of ischemia/reperfusion brain injury.Microdialysis allows for the direct measurement of extracellular molecules in an attempt to characterize metabolic derangements before they become clinically relevant. Advancements in technology have allowed for the bedside assay of multiple markers of ischemia and metabolic dysfunction, and the applications for traumatic brain injury have been well established. As clinicians become more comfortable with these tools their widespread use and potential for clinical impact with continue to rise. PMID:27604731

  14. Urine Output Changes During Postcardiac Arrest Therapeutic Hypothermia.

    PubMed

    Raper, Jaron D; Wang, Henry E

    2013-12-01

    While commonly described, no studies have characterized cold-induced diuresis or rewarm anti-diuresis occurring during the delivery of therapeutic hypothermia (TH). We sought to determine urine output changes during the provision of postcardiac arrest TH. We analyzed clinical data on patients receiving postcardiac arrest TH at an urban tertiary care center. TH measures included cooling by cold intravenous fluid, external ice packs, and a commercial external temperature management system. TH treatment was divided into phases: (1) induction, (2) maintenance, (3) rewarm, and (4) post-rewarm. The primary outcome measure was the mean urine output rate (mL/hour). We compared urine output rates between TH phases using a Generalized Estimating Equations model, defining urine output rate (mL/hour) as the dependent variable and TH phase (induction, maintenance, rewarm, and post-rewarm) as the primary exposure variable. We adjusted for age, sex, initial ECG rhythm, location of arrest, shock, acute kidney injury, rate of intravenous fluid input, and body mass index. Complete urine output data were available on 33 patients. Mean urine output rates during induction, maintenance, rewarm, and post-rewarm phases were 157 mL/hour (95% CI: 104-210), 103 mL/hour (95% CI: 82-125), 70 mL/hour (95% CI: 51-88), and 91 mL/hour (95% CI: 65-117), respectively. Compared with the post-rewarm phase, adjusted urine output was higher during the TH induction phase (output rate difference +51 mL/hour; 95% CI: 3-99). Adjusted urine output during the maintenance and rewarm phases did not differ from the post-rewarm phase. In this preliminary study, we observed modest increases in urine output during TH induction. We did not observe urine output changes during TH maintenance or rewarming. PMID:24380030

  15. Motion sickness increases the risk of accidental hypothermia.

    PubMed

    Nobel, Gerard; Eiken, Ola; Tribukait, Arne; Kölegård, Roger; Mekjavic, Igor B

    2006-09-01

    Motion sickness (MS) has been found to increase body-core cooling during immersion in 28 degrees C water, an effect ascribed to attenuation of the cold-induced peripheral vasoconstriction (Mekjavic et al. in J Physiol 535(2):619-623, 2001). The present study tested the hypothesis that a more profound cold stimulus would override the MS effect on peripheral vasoconstriction and hence on the core cooling rate. Eleven healthy subjects underwent two separate head-out immersions in 15 degrees C water. In the control trial (CN), subjects were immersed after baseline measurements. In the MS-trial, subjects were rendered motion sick prior to immersion, by using a rotating chair in combination with a regimen of standardized head movements. During immersion in the MS-trial, subjects were exposed to an optokinetic stimulus (rotating drum). At 5-min intervals subjects rated their temperature perception, thermal comfort and MS discomfort. During immersion mean skin temperature, rectal temperature, the difference in temperature between the non-immersed right forearm and 3rd finger of the right hand (DeltaTff), oxygen uptake and heart rate were recorded. In the MS-trial, rectal temperature decreased substantially faster (33%, P < 0.01). Also, the DeltaTff response, an index of peripheral vasomotor tone, as well as the oxygen uptake, indicative of the shivering response, were significantly attenuated (P < 0.01 and P < 0.001, respectively) by MS. Thus, MS may predispose individuals to hypothermia by enhancing heat loss and attenuating heat production. This might have significant implications for survival in maritime accidents. PMID:16847677

  16. Highlights in basic autonomic neurosciences: Central adenosine A1 receptor – The key to a hypometabolic state and therapeutic hypothermia?

    PubMed Central

    Tupone, D.; Madden, C.J.; Morrison, S.F.

    2016-01-01

    The positive outcome that hypothermia contributes to brain and cardiac protection following ischemia has stimulated research in the development of pharmacological approaches to induce a hypothermic/hypometabolic state. Here we review three papers to highlight the role of the adenosine 1 receptor (A1AR) as a potential mediator and physiological regulator of a hypothermic state in both hibernating and non-hibernating mammals. We would like to emphasize the importance of comparative studies between hibernating and non-hibernating species that could lead to important discoveries on the mechanisms inducing hibernation and how they might be translated to induce a clinically useful hypothermic state. PMID:23465354

  17. The Social Epidemiology of Accidental Hypothermia among the Aged.

    ERIC Educational Resources Information Center

    Rango, Nicholas

    1985-01-01

    Describes the 1970-1979 incidence of exposure-related hypothermia deaths in the United States. Showed nonwhite men at highest and white women at lowest risk at all ages. Age-related impairment in theromoregulation, functional disability, poverty, and social isolation were found to increase elderly individual's susceptibility to this environmental…

  18. Prevention and Management of Neonatal Hypothermia in Rural Zambia

    PubMed Central

    Lunze, Karsten; Yeboah-Antwi, Kojo; Marsh, David R.; Kafwanda, Sarah Ngolofwana; Musso, Austen; Semrau, Katherine; Waltensperger, Karen Z.; Hamer, Davidson H.

    2014-01-01

    Background Neonatal hypothermia is increasingly recognized as a risk factor for newborn survival. The World Health Organization recommends maintaining a warm chain and skin-to-skin care for thermoprotection of newborn children. Since little is known about practices related to newborn hypothermia in rural Africa, this study's goal was to characterize relevant practices, attitudes, and beliefs in rural Zambia. Methods and Findings We conducted 14 focus group discussions with mothers and grandmothers and 31 in-depth interviews with community leaders and health officers in Lufwanyama District, a rural area in the Copperbelt Province, Zambia, enrolling a total of 171 participants. We analyzed data using domain analysis. In rural Lufwanyama, community members were aware of the danger of neonatal hypothermia. Caregivers' and health workers' knowledge of thermoprotective practices included birthplace warming, drying and wrapping of the newborn, delayed bathing, and immediate and exclusive breastfeeding. However, this warm chain was not consistently maintained in the first hours postpartum, when newborns are at greatest risk. Skin-to-skin care was not practiced in the study area. Having to assume household and agricultural labor responsibilities in the immediate postnatal period was a challenge for mothers to provide continuous thermal care to their newborns. Conclusions Understanding and addressing community-based practices on hypothermia prevention and management might help improve newborn survival in resource-limited settings. Possible interventions include the implementation of skin-to-skin care in rural areas and the use of appropriate, low-cost newborn warmers to prevent hypothermia and support families in their provision of newborn thermal protection. Training family members to support mothers in the provision of thermoprotection for their newborns could facilitate these practices. PMID:24714630

  19. Incidence and effect of hypothermia in seriously injured patients.

    PubMed

    Luna, G K; Maier, R V; Pavlin, E G; Anardi, D; Copass, M K; Oreskovich, M R

    1987-09-01

    Hypothermia is a well recognized consequence of severe injury, even in temperate climates, and the physiologic consequences of hypothermia are known to be detrimental. To analyze the frequency and risk factors for hypothermia and its effect on patient outcome, we prospectively studied 94 intubated injured patients at a regional trauma center during a 16-month period. Esophageal temperature probes were placed in the field or ER and core temperatures (T) were followed for 24 hours or until rewarming. Patients were designated as normothermic (greater than 36 degrees C), mildly hypothermic (34 degrees C-36 degrees C) or severely hypothermic (less than 34 degrees C) based on initial T. The risk factors for hypothermia evaluated included age, severity and location of injuries, blood alcohol level, blood transfusion requirements, and time spent in the field, ER, or OR. The average initial T was 35 degrees C, with no seasonal variation. Injury severity and survival correlated with severe hypothermia. Normothermic patients had an average ISS of 28 with a 78% survival. Severely hypothermic patients had an average ISS of 36 with a 41% survival (p less than 0.05). Patient age strongly correlated with outcome although there was no relationship between age and initial temperature. Sixty-two per cent of patients tested were positive for blood alcohol, and one half were legally intoxicated (BAC greater than 100 mg%). However, no consistent correlation was found between alcohol intoxication and initial temperature or patient survival. Blood transfusion requirements paralleled injury severity and patients receiving greater than 10 unit transfusions had significantly lower core temperature (p less than 0.05). The average temperature change was positive in the ER, OR, and ICU with time to rewarming correlating with the aggressiveness of warming measures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3656463

  20. Therapeutic hypothermia for the treatment of acute myocardial infarction-combined analysis of the RAPID MI-ICE and the CHILL-MI trials.

    PubMed

    Erlinge, David; Götberg, Matthias; Noc, Marko; Lang, Irene; Holzer, Michael; Clemmensen, Peter; Jensen, Ulf; Metzler, Bernhard; James, Stefan; Bøtker, Hans Erik; Omerovic, Elmir; Koul, Sasha; Engblom, Henrik; Carlsson, Marcus; Arheden, Håkan; Östlund, Ollie; Wallentin, Lars; Klos, Bradley; Harnek, Jan; Olivecrona, Göran K

    2015-06-01

    In the randomized rapid intravascular cooling in myocardial infarction as adjunctive to percutaneous coronary intervention (RAPID MI-ICE) and rapid endovascular catheter core cooling combined with cold saline as an adjunct to percutaneous coronary intervention for the treatment of acute myocardial infarction CHILL-MI studies, hypothermia was rapidly induced in conscious patients with ST-elevation myocardial infarction (STEMI) by a combination of cold saline and endovascular cooling. Twenty patients in RAPID MI-ICE and 120 in CHILL-MI with large STEMIs, scheduled for primary percutaneous coronary intervention (PCI) within <6 hours after symptom onset were randomized to hypothermia induced by rapid infusion of 600-2000 mL cold saline combined with endovascular cooling or standard of care. Hypothermia was initiated before PCI and continued for 1-3 hours after reperfusion aiming at a target temperature of 33°C. The primary endpoint was myocardial infarct size (IS) as a percentage of myocardium at risk (IS/MaR) assessed by cardiac magnetic resonance imaging at 4±2 days. Patients randomized to hypothermia treatment achieved a mean core body temperature of 34.7°C before reperfusion. Although significance was not achieved in CHILL-MI, in the pooled analysis IS/MaR was reduced in the hypothermia group, relative reduction (RR) 15% (40.5, 28.0-57.6 vs. 46.6, 36.8-63.8, p=0.046, median, interquartile range [IQR]). IS/MaR was predominantly reduced in early anterior STEMI (0-4h) in the hypothermia group, RR=31% (40.5, 28.8-51.9 vs. 59.0, 45.0-67.8, p=0.01, median, IQR). There was no mortality in either group. The incidence of heart failure was reduced in the hypothermia group (2 vs. 11, p=0.009). Patients with large MaR (>30% of the left ventricle) exhibited significantly reduced IS/MaR in the hypothermia group (40.5, 27.0-57.6 vs. 55.1, 41.1-64.4, median, IQR; hypothermia n=42 vs. control n=37, p=0.03), while patients with MaR<30% did not show effect of hypothermia (35

  1. Effect of haemodilution, acidosis, and hypothermia on the activity of recombinant factor VIIa (NovoSeven®)

    PubMed Central

    Viuff, D.; Lauritzen, B.; Pusateri, A. E.; Andersen, S.; Rojkjaer, R.; Johansson, P. I.

    2008-01-01

    Background A range of plasma volume expanders is used clinically, often in settings where haemostasis may already be impaired. The haemostatic agent, recombinant activated factor VII (rFVIIa, NovoSeven®), may be used to improve haemostasis but potential interactions with different volume expanders are poorly understood. Methods Clot formation was measured by thromboelastography (TEG) using blood from healthy volunteers. In vitro effects of rFVIIa with haemodilution, acidosis, and hypothermia were examined. Conditions were induced by dilution with NaCl (0.9%), lactated Ringer's solution, albumin 5%, or hydroxyethyl starch (HES) solutions [MW (molecular weight) 130–670 kDa]; by adjusting pH to 6.8 with 1 M HEPES (N-2-hydroxyethylpiperazine-N′-2-ethanesulphonic acid) buffer; or by reducing temperature to 32°C. We also studied the effect of low vs high MW HES (MW 200 vs 600 kDa) and rFVIIa on in vivo bleeding time (BT) in rabbits. Results Haemodilution progressively altered TEG parameters. rFVIIa improved TEG parameters in the presence of acidosis, hypothermia or 20% haemodilution (P<0.05). At 40% haemodilution, the rFVIIa effect was diminished particularly with high MW HES. In vivo, rFVIIa shortened the BT (P<0.05) with low but not high MW HES. Conclusions Efficacy of rFVIIa was affected by the degree of haemodilution and type of volume expander, but not by acidosis or hypothermia. PMID:18565966

  2. Prolonged Local Hypothermia Has No Long-Term Adverse Effect on the Spinal Cord

    PubMed Central

    Vipin, Ashwati; Kortelainen, Jukka; Al-Nashash, Hasan; Chua, Soo Min; Thow, Xinyuan; Manivannan, Janani; Astrid; Thakor, Nitish V.; Kerr, Candace L.

    2015-01-01

    Hypothermia is known to be neuroprotective and is one of the most effective and promising first-line treatments for central nervous system (CNS) trauma. At present, induction of local hypothermia, as opposed to general hypothermia, is more desired because of its ease of application and safety; fewer side effects and an absence of severe complications have been noted. Local hypothermia involves temperature reduction of a small and specific segment of the spinal cord. Our group has previously shown the neuroprotective effect of short-term, acute moderate general hypothermia through improvements in electrophysiological and motor behavioral assessments, as well as histological examination following contusive spinal cord injury (SCI) in rats. We have also shown the benefit of using short-term local hypothermia versus short-term general hypothermia post-acute SCI. The overall neuroprotective benefit of hypothermia can be categorized into three main components: (1) induction modality, general versus local, (2) invasive, semi-invasive or noninvasive, and (3) duration of hypothermia induction. In this study, a series of experiments were designed to investigate the feasibility, long-term safety, as well as eventual complications and side effects of prolonged, semi-invasive, moderate local hypothermia (30°C±0.5°C for 5 and 8 hours) in rats with uninjured spinal cord while maintaining their core temperature at 37°C±0.5°C. The weekly somatosensory evoked potential and motor behavioral (Basso, Beattie and Bresnahan) assessments of rats that underwent 5 and 8 hours of semi-invasive local hypothermia, which revealed no statistically significant changes in electrical conductivity and behavioral outcomes. In addition, 4 weeks after local hypothermia induction, histological examination showed no anatomical damages or morphological changes in their spinal cord structure and parenchyma. We concluded that this method of prolonged local hypothermia is feasible, safe, and has the

  3. The Use of Hypothermia Therapy in Traumatic Ischemic/Reperfusional Brain Injury: Review of the Literatures

    PubMed Central

    Frantzen, Janek; Bullock, Ross; Gajavelli, Shyam; Burks, Stephen; Bramlett, Helen; Dietrich, W. Dalton

    2011-01-01

    Therapeutic mild hypothermia has been widely used in brain injury. It has been evaluated in numerous clinical trials, and there is strong evidence for the use of hypothermia in treating patients with several types of ischemic/reperfusional (I/R) injuries, the examples being cardiac arrest and neonatal hypoxic-ischemic encephalopathy. In spite of many basic research projects demonstrating effectiveness, therapeutic hypothermia has not been proved effective for the heterogeneous group of patients with traumatic brain injury (TBI) in multicenter clinical trials. In the latest clinical trial, however, researchers were able to demonstrate the significant beneficial effects of hypothermia in one specific group; patients with mass evacuated lesions. This suggested that mild therapeutic hypothermia might be effective for I/R related TBI. In this article, we have reviewed much of the previous literature concerning the mechanisms of I/R injury to the protective effects of mild therapeutic hypothermia. PMID:23439678

  4. Therapeutic hypothermia after cardiac arrest and myocardial infarction.

    PubMed

    Holzer, Michael; Behringer, Wilhelm

    2008-12-01

    About 17 million people worldwide die from cardiovascular diseases each year. Impaired neurologic function after sudden cardiac arrest is a major cause of death in these patients. Up to now, no specific post-arrest therapy was available to improve outcome. Recently, two randomized clinical trials of mild therapeutic hypothermia after successful resuscitation from cardiac arrest showed improvement of neurological outcome and reduced mortality. A broad implementation of this new therapy could save thousands of lives worldwide, as only 6 patients have to be treated to get one additional patient with favourable neurological recovery. At present, myocardial reperfusion by thrombolytic therapy or primary PCI as early as possible is the most effective therapy in patients with acute myocardial infarction. Mild therapeutic hypothermia might be a promising new therapy to prevent reperfusion injury after myocardial infarction, but its use in daily clinical routine cannot be recommended with the available evidence. PMID:19137812

  5. Tolerance to ethanol hypothermia in HOT and COLD mice.

    PubMed

    Crabbe, J C

    1994-02-01

    COLD and HOT mice have been selected to be sensitive or resistant, respectively, to the acute hypothermic effect of ethanol. Previous studies have found HOT mice to be relatively resistant to the development of tolerance to this effect, whereas COLD mice readily develop tolerance. By administering several doses of ethanol and recording multiple postdrug temperatures, in the current study we equated the selected lines for area under the curve describing initial hypothermic response over time, a measure reflecting both maximal hypothermia achieved and the duration of total hypothermic response. The dose-response function for COLD mice was much steeper than that for HOT mice, and HOT mice recovered to baseline body temperatures more slowly. Doses were administered daily for 5 days. Both lines developed tolerance to ethanol hypothermia. The magnitude of tolerance developed was greater in COLD than in HOT mice. At higher doses, HOT mice showed a progressively enhanced hypothermic response over days (i.e., sensitization). PMID:8198225

  6. Selective hypothermia in repair of aneurysms of the descending aorta.

    PubMed Central

    Cooley, D A; Boyer, J W

    1999-01-01

    Since 1991, we have used a simple, single-clamp technique with open distal anastomosis to repair aneurysms of the descending aorta. To enhance the results of the single-clamp technique in a recent high-risk patient, we used selective hypothermia, cooling primarily the tissues and organs supplied by the aorta and tributaries distal to the left subclavian artery. This preliminary report describes the technique and gives the rationale for its use. PMID:10397431

  7. Hypothermia improves oral and gastric mucosal microvascular oxygenation during hemorrhagic shock in dogs.

    PubMed

    Vollmer, Christian; Schwartges, Ingo; Swertz, Meike; Beck, Christopher; Bauer, Inge; Picker, Olaf

    2013-01-01

    Hypothermia is known to improve tissue function in different organs during physiological and pathological conditions. The aim of this study was to evaluate the effects of hypothermia on oral and gastric mucosal microvascular oxygenation (μHbO2) and perfusion (μflow) under physiological and hemorrhagic conditions. Five dogs were repeatedly anesthetized. All animals underwent each experimental protocol (randomized cross-over design): hypothermia (34°C), hypothermia during hemorrhage, normothermia, and normothermia during hemorrhage. Microcirculatory and hemodynamic variables were recorded. Systemic (DO2) and oral mucosal (μDO2) oxygen delivery were calculated. Hypothermia increased oral μ HbO2 with no effect on gastric μHbO2. Hemorrhage reduced oral and gastric μHbO2 during normothermia (-36 ± 4% and -27 ± 7%); however, this effect was attenuated during additional hypothermia (-15 ± 5% and -11 ± 5%). The improved μ HbO2 might be based on an attenuated reduction in μ flow during hemorrhage and additional hypothermia (-51 ± 21 aU) compared to hemorrhage and normothermia (-106 ± 19 aU). μDO2 was accordingly attenuated under hypothermia during hemorrhage whereas DO2 did not change. Thus, in this study hypothermia alone improves oral μHbO2 and attenuates the effects of hemorrhage on oral and gastric μ HbO2. This effect seems to be mediated by an increased μDO2 on the basis of increased μ flow. PMID:24327826

  8. The neurovascular protection afforded by delayed local hypothermia after transient middle cerebral artery occlusion.

    PubMed

    Kim, Jong-Heon; Seo, Minchul; Han, Hyung Soo; Park, Jaechan; Suk, Kyoungho

    2013-05-01

    Therapeutic hypothermia is a robust therapeutic tool in experimental stroke models but its clinical applications are limited. Furthermore, optimal conditions for therapeutic hypothermia, such as, temperature and the initiation and duration of cooling must be individualized. Here, we evaluated the therapeutic effects of delayed local hypothermia, administered for 44 hr after 4 hr of reperfusion in a rat model of transient middle cerebral artery occlusion (tMCAo), using a cooling device that allowed controlled local hypothermia (31 °C) in brain. Histological data revealed that local hypothermia significantly reduced infarct volumes and glial hypertrophic activation. Brain water contents, IgG leakage, and Evans Blue extravasation were notably reduced by local hypothermia. Furthermore, local hypothermia had strong vasculoprotective effects, as determined by immunohistochemistry and Western blot analyses for endothelial barrier antigen (EBA), laminin, aquaporin-4, and tight junction proteins in brain. Our data indicate that delayed/prolonged local hypothermia confers neurovascular protection, reduces brain edema, and inhibits inflammatory glial activation, and suggest that hypothermic conservation of vascular structures and functions account for the therapeutic effects of local hypothermia observed in this model of experimental stroke. PMID:23469955

  9. Therapeutic hypothermia after cardiac arrest and return of spontaneous circulation: it's complicated.

    PubMed

    Beseda, Ryan; Smith, Susan; Veenstra, Amy

    2014-12-01

    Providing evidence-based care to patients with return of spontaneous circulation after a cardiac arrest is a recent complex innovation. Once resuscitated patients must be assessed for appropriateness for therapeutic hypothermia, be cooled in a timely manner, maintained while hypothermic, rewarmed within a specified time frame, and then assessed for whether hypothermia was successful for the patient through neuroprognostication. Nurses caring for therapeutic hypothermia patients must be knowledgeable and prepared to provide care to the patient and family. This article provides an overview of the complexity of therapeutic hypothermia for patients with return of spontaneous circulation in the form of a case study. PMID:25438893

  10. Isolation Syndrome after Cardiac Arrest and Therapeutic Hypothermia

    PubMed Central

    Forgacs, Peter B.; Fridman, Esteban A.; Goldfine, Andrew M.; Schiff, Nicholas D.

    2016-01-01

    Here, we present the first description of an isolation syndrome in a patient who suffered prolonged cardiac arrest and underwent a standard therapeutic hypothermia protocol. Two years after the arrest, the patient demonstrated no motor responses to commands, communication capabilities, or visual tracking at the bedside. However, resting neuronal metabolism and electrical activity across the entire anterior forebrain was found to be normal despite severe structural injuries to primary motor, parietal, and occipital cortices. In addition, using quantitative electroencephalography, the patient showed evidence for willful modulation of brain activity in response to auditory commands revealing covert conscious awareness. A possible explanation for this striking dissociation in this patient is that altered neuronal recovery patterns following therapeutic hypothermia may lead to a disproportionate preservation of anterior forebrain cortico-thalamic circuits even in the setting of severe hypoxic injury to other brain areas. Compared to recent reports of other severely brain-injured subjects with such dissociation of clinically observable (overt) and covert behaviors, we propose that this case represents a potentially generalizable mechanism producing an isolation syndrome of blindness, motor paralysis, and retained cognition as a sequela of cardiac arrest and therapeutic hypothermia. Our findings further support that highly-preserved anterior cortico-thalamic integrity is associated with the presence of conscious awareness independent from the degree of injury to other brain areas. PMID:27375420

  11. Repeated administration of phytocannabinoid Δ(9)-THC or synthetic cannabinoids JWH-018 and JWH-073 induces tolerance to hypothermia but not locomotor suppression in mice, and reduces CB1 receptor expression and function in a brain region-specific manner.

    PubMed

    Tai, S; Hyatt, W S; Gu, C; Franks, L N; Vasiljevik, T; Brents, L K; Prather, P L; Fantegrossi, W E

    2015-12-01

    These studies probed the relationship between intrinsic efficacy and tolerance/cross-tolerance between ∆(9)-THC and synthetic cannabinoid drugs of abuse (SCBs) by examining in vivo effects and cellular changes concomitant with their repeated administration in mice. Dose-effect relationships for hypothermic effects were determined in order to confirm that SCBs JWH-018 and JWH-073 are higher efficacy agonists than ∆(9)-THC in mice. Separate groups of mice were treated with saline, sub-maximal hypothermic doses of JWH-018 or JWH-073 (3.0mg/kg or 10.0mg/kg, respectively) or a maximally hypothermic dose of 30.0mg/kg ∆(9)-THC once per day for 5 consecutive days while core temperature and locomotor activity were monitored via biotelemetry. Repeated administration of all drugs resulted in tolerance to hypothermic effects, but not locomotor effects, and this tolerance was still evident 14 days after the last drug administration. Further studies treated mice with 30.0mg/kg ∆(9)-THC once per day for 4 days, then tested with SCBs on day 5. Mice with a ∆(9)-THC history were cross-tolerant to both SCBs, and this cross-tolerance also persisted 14 days after testing. Select brain regions from chronically treated mice were examined for changes in CB1 receptor expression and function. Expression and function of hypothalamic CB1Rs were reduced in mice receiving chronic drugs, but cortical CB1R expression and function were not altered. Collectively, these data demonstrate that repeated ∆(9)-THC, JWH-018 and JWH-073 can induce long-lasting tolerance to some in vivo effects, which is likely mediated by region-specific downregulation and desensitization of CB1Rs. PMID:26361728

  12. Effect of wet-cold weather transportation conditions on thermoregulation and the development of accidental hypothermia in pullets under tropical conditions.

    PubMed

    Minka, Ndazo S; Ayo, Joseph O

    2016-03-01

    The present study examines onboard thermal microclimatic conditions and thermoregulation of pullets exposed to accidental hypothermia during wet-cold weather transportation conditions, and the effect of rewarming on colonic temperature (CT) of the birds immediately after transportation. A total of 2200 pullets were transportation for 5 h in two separate vehicles during the nighttime. The last 3 h of the transportation period was characterized by heavy rainfall. During the precipitation period, each vehicle was covered one fourth way from the top-roof with a tarpaulin. The onboard thermal conditions inside the vehicles during transportation, which comprised ambient temperature and relative humidity were recorded, while humidity ratio and specific enthalpy were calculated. The CT of the birds was recorded before and after transportation. During transportation, onboard thermal heterogeneity was observed inside the vehicles with higher (p < 0.05) values in the front and center, and lower values recorded at the air inlets at the sides and rear planes. The CT values recorded in birds at the front and center planes were between 42.2 and 42.5 °C, indicative of mild hypothermia; while lower CT values between 28 and 38 °C were recorded at the sides and rear planes, indicative of mild to severe hypothermia. Several hours of gradual rewarming returned the CT to normal range. The result, for the first time, demonstrated the occurrence of accidental hypothermia in transported pullets under tropical conditions and a successful rewarming outcome. In conclusion, transportation of pullets during wet weather at onboard temperature of 18-20 °C induced hypothermia on birds located at the air inlets, which recovered fully after several hours of gradual rewarming. PMID:26198381

  13. Effect of wet-cold weather transportation conditions on thermoregulation and the development of accidental hypothermia in pullets under tropical conditions

    NASA Astrophysics Data System (ADS)

    Minka, Ndazo S.; Ayo, Joseph O.

    2016-03-01

    The present study examines onboard thermal microclimatic conditions and thermoregulation of pullets exposed to accidental hypothermia during wet-cold weather transportation conditions, and the effect of rewarming on colonic temperature (CT) of the birds immediately after transportation. A total of 2200 pullets were transportation for 5 h in two separate vehicles during the nighttime. The last 3 h of the transportation period was characterized by heavy rainfall. During the precipitation period, each vehicle was covered one fourth way from the top-roof with a tarpaulin. The onboard thermal conditions inside the vehicles during transportation, which comprised ambient temperature and relative humidity were recorded, while humidity ratio and specific enthalpy were calculated. The CT of the birds was recorded before and after transportation. During transportation, onboard thermal heterogeneity was observed inside the vehicles with higher ( p < 0.05) values in the front and center, and lower values recorded at the air inlets at the sides and rear planes. The CT values recorded in birds at the front and center planes were between 42.2 and 42.5 °C, indicative of mild hypothermia; while lower CT values between 28 and 38 °C were recorded at the sides and rear planes, indicative of mild to severe hypothermia. Several hours of gradual rewarming returned the CT to normal range. The result, for the first time, demonstrated the occurrence of accidental hypothermia in transported pullets under tropical conditions and a successful rewarming outcome. In conclusion, transportation of pullets during wet weather at onboard temperature of 18-20 °C induced hypothermia on birds located at the air inlets, which recovered fully after several hours of gradual rewarming.

  14. Therapeutic hypothermia impacts leukocyte kinetics after cardiac arrest

    PubMed Central

    Dufner, Matthias C.; Andre, Florian; Stiepak, Jan; Zelniker, Thomas; Chorianopoulos, Emmanuel; Preusch, Michael; Katus, Hugo A.

    2016-01-01

    Background Patients admitted to the hospital after primarily successful cardiopulmonary resuscitation (CPR) are at a very high risk for neurologic deficits and death. Targeted temperature management (TTM) for mild therapeutic hypothermia has been shown to improve survival compared to standard treatment. Acute cardiovascular events, such as myocardial infarction (MI), are a major cause for cardiac arrest (CA) in patients who undergo CPR. Recent findings have demonstrated the importance and impact of the leukocyte response following acute MI. Methods In this retrospective, single center study we enrolled 169 patients with CA due to non-traumatic causes and primarily successful CPR. A total of 111 subjects (66%) underwent TTM aiming for a target temperature of 32–34 °C. Results Analysis of 30 day follow up showed a significantly improved survival of all patients who received TTM compared to patients without hypothermia (P=0.0001). Furthermore TTM was an independent variable of good neurological outcome after 6 months (P=0.0030). Therapeutic hypothermia was found to be beneficial independent of differences in age and sex between both groups. While a higher rate of pneumonia was observed with TTM, this diagnosis had no additional impact on survival or neurological outcome. The beneficial effect on mortality remained significant in patients with the diagnosis of an acute cardiac event (P=0.0145). Next, we evaluated the kinetics of leukocytes in this group over the course of 7 days after CA. At presentation, patients showed a mean level of 16.5±6.7 of leukocytes per microliter. While this level stayed stable in the group of patients without hypothermia, patients who received TTM showed a significant decline of leukocyte levels resulting in significantly lower numbers of leukocytes on days 3 and 5 after CPR. Interestingly, these differences in leukocyte counts remained beyond the time period of TTM while C-reactive protein (CRP) levels were suppressed only during

  15. Therapeutic Hypothermia after Prolonged Cardiac Arrest: Case Report with Review of Literature

    PubMed Central

    Yadav, Sankalp; Garg, Nitin

    2015-01-01

    Patients who survive cardiac arrest often develop severe neurological dysfunction due to the hypoxic brain injury and reperfusion induced cell death. Therapeutic hypothermia (TH) has become a standard therapy of cerebral protection following the successful return of spontaneous circulation in patients of out-of-hospital cardiac arrest, according to American heart association guidelines. This is a case report of a 30-year-old patient who developed in-hospital cardiac arrest and was revived after prolonged cardiopulmonary resuscitation (CPR) and also required primary angioplasty. TH was then established with local measures for 24 hours for cerebral protection. The patient was gradually and successfully weaned off from ventilator with no neurological impairment. There is an increasing evidence of TH and its protective mechanisms in patients with non-shockable arrest rhythms with particular emphasis on neurological outcomes. This article emphasizes the role of TH in every successful CPR irrespective of the cardiac rhythm. PMID:26500937

  16. The geography of hypothermia in the United States: An analysis of mortality, morbidity, thresholds, and messaging

    NASA Astrophysics Data System (ADS)

    Spencer, Jeremy M.

    Hypothermia within the United States has seldom been studied from a geographic perspective. This dissertation assessed the following aspects of hypothermia: 1) A cataloging of Internet web pages containing hypothermia-related guidance, with a summary of the information contained within. The summarized hypothermia information was assessed for scientific validity through an extensive assessment of the peer-reviewed medical literature; 2) the spatio-temporal distribution of hypothermia deaths in U.S. Combined Statistical areas for the years 1979-2004, and their association with National Weather Service windchill advisory and warning thresholds; 3) the spatio-temporal distribution of hypothermia morbidity in the State of New York from 1991-1992 to 2005-2006 and its association with Spatial Synoptic Classification weather types. The results indicate that web-based hypothermia information has generally poor content not supported by the scientific literature, and there are many prominent omissions of well-established hypothermia information. A total of 9,185 hypothermia fatalities attributable to cold exposure occurred in 89 metro areas from 1979 to 2004. The southeastern US had the greatest vulnerability to hypothermia, with high rates of deaths occurring at higher temperatures than northern states. Median windchill temperature associated with deaths was generally latitudinal, with southern deaths occurring at higher temperatures. For all regions, hypothermia deaths occurred at temperatures considerably higher than windchill advisory criteria. Hypothermia morbidity within New York State was associated with long-lasting polar weather types. There are a number of findings common to these three papers. Information about hypothermia tends to be under-communicated (no central location for wind chill alerts, unsupported statements on many websites). Hypothermia deaths and hospitalizations increase when locally cold and long-lasting weather types occur, which fits in with what

  17. Insufficient glucose supply is linked to hypothermia upon cold exposure in high-fat diet-fed mice lacking PEMT[S

    PubMed Central

    Gao, Xia; van der Veen, Jelske N.; Fernandez-Patron, Carlos; Vance, Jean E.; Vance, Dennis E.; Jacobs, René L.

    2015-01-01

    Mice that lack phosphatidylethanolamine N-methyltransferase (Pemt−/− mice) are protected from high-fat (HF) diet-induced obesity. HF-fed Pemt−/− mice show higher oxygen consumption and heat production, indicating that more energy might be utilized for thermogenesis and might account for the resistance to diet-induced weight gain. To test this hypothesis, HF-fed Pemt−/− and Pemt+/+ mice were challenged with acute cold exposure at 4°C. Unexpectedly, HF-fed Pemt−/− mice developed hypothermia within 3 h of cold exposure. In contrast, chow-fed Pemt−/− mice, possessing similar body mass, maintained body temperature. Lack of PEMT did not impair the capacity for thermogenesis in skeletal muscle or brown adipose tissue. Plasma catecholamines were not altered by Pemt genotype, and stimulation of lipolysis was intact in brown and white adipose tissue of Pemt−/− mice. HF-fed Pemt−/− mice also developed higher systolic blood pressure, accompanied by reduced cardiac output. Choline supplementation reversed the cold-induced hypothermia in HF-fed Pemt−/− mice with no effect on blood pressure. Plasma glucose levels were ∼50% lower in HF-fed Pemt−/− mice compared with Pemt+/+ mice. Choline supplementation normalized plasma hypoglycemia and the expression of proteins involved in gluconeogenesis. We propose that cold-induced hypothermia in HF-fed Pemt−/− mice is linked to plasma hypoglycemia due to compromised hepatic glucose production. PMID:26113536

  18. Spontaneous hypothermia in human sepsis is a transient, self-limiting, and nonterminal response.

    PubMed

    Fonseca, Monique T; Rodrigues, Abner C; Cezar, Luana C; Fujita, Andre; Soriano, Francisco G; Steiner, Alexandre A

    2016-06-15

    Hypothermia in sepsis is generally perceived as something dysregulated and progressive although there has been no assessment on the natural course of this phenomenon in humans. This was the first study on the dynamics of hypothermia in septic patients not subjected to active rewarming, and the results were surprising. A sample of 50 subjects presenting with spontaneous hypothermia during sepsis was drawn from the 2005-2012 database of an academic hospital. Hypothermia was defined as body temperature below 36.0°C for longer than 2 h, with at least one reading of 35.5°C or less. The patients presented with 138 episodes of hypothermia, 21 at the time of the sepsis diagnosis and 117 with a later onset. However, hypothermia was uncommon in the final 12 h of life of the patients that succumbed. The majority (97.1%) of the hypothermic episodes were transient and self-limited; the median recovery time was 6 h; body temperature rarely fell below 34.0°C. Bidirectional oscillations in body temperature were evident in the course of hypothermia. Nearly half of the hypothermic episodes had onset in the absence of shock or respiratory distress, and the incidence of hypothermia was not increased during either of these conditions. Usage of antipyretic drugs, sedatives, neuroleptics, or other medications did not predict the onset of hypothermia. In conclusion, hypothermia appears to be a predominantly transient, self-limiting, and nonterminal phenomenon that is inherent to human sepsis. These characteristics resemble those of the regulated hypothermia shown to replace fever in animal models of severe systemic inflammation. PMID:26989218

  19. Effect of an imidazobenzodiazepine, Ro15-4513, on the incoordination and hypothermia produced by ethanol and pentobarbital.

    PubMed

    Hoffman, P L; Tabakoff, B; Szabó, G; Suzdak, P D; Paul, S M

    1987-08-01

    The imidazobenzodiazepine, Ro15-4513, which is a partial inverse agonist at brain benzodiazepine receptors, reversed the incoordinating effect of ethanol in mice, as measured on an accelerating Rotarod. This effect was blocked by benzodiazepine receptor antagonists. In contrast, Ro15-4513 had no effect on ethanol-induced hypothermia in mice. However, Ro15-4513 reversed the hypothermic effect of pentobarbital, and, at a higher dose, also reversed the incoordinating effect of pentobarbital in mice. The data support the hypothesis that certain of the pharmacological effects of ethanol are mediated by actions at the GABA-benzodiazepine receptor-coupled chloride channel. PMID:3600196

  20. Extracranial Hypothermia During Cardiac Arrest and Cardiopulmonary Resuscitation Is Neuroprotective In Vivo

    PubMed Central

    Fujiyoshi, Tetsuhiro; Koerner, Ines P.; Herson, Paco S.

    2014-01-01

    There is increasing evidence that ischemic brain injury is modulated by peripheral signaling. Peripheral organ ischemia can induce brain inflammation and injury. We therefore hypothesized that brain injury sustained after cardiac arrest (CA) is influenced by peripheral organ ischemia and that peripheral organ protection can reduce brain injury after CA and cardiopulmonary resuscitation (CPR). Male C57Bl/6 mice were subjected to CA/CPR. Brain temperature was maintained at 37.5°C±0.0°C in all animals. Body temperature was maintained at 35.1°C±0.1°C (normothermia) or 28.8°C±1.5°C (extracranial hypothermia [ExHy]) during CA. Body temperature after resuscitation was maintained at 35°C in all animals. Behavioral testing was performed at 1, 3, 5, and 7 days after CA/CPR. Either 3 or 7 days after CA/CPR, blood was analyzed for serum urea nitrogen, creatinine, alanine aminotransferase, aspartate aminotransferase, and interleukin-1β; mice were euthanized; and brains were sectioned. CA/CPR caused peripheral organ and brain injury. ExHy animals experienced transient reduction in brain temperature after resuscitation (2.1°C±0.5°C for 4 minutes). Surprisingly, ExHy did not change peripheral organ damage. In contrast, hippocampal injury was reduced at 3 days after CA/CPR in ExHy animals (22.4%±6.2% vs. 45.7%±9.1%, p=0.04, n=15/group). This study has two main findings. Hypothermia limited to CA does not reduce peripheral organ injury. This unexpected finding suggests that after brief ischemia, such as during CA/CPR, signaling or events after reperfusion may be more injurious than those during the ischemic period. Second, peripheral organ hypothermia during CA reduces hippocampal injury independent of peripheral organ protection. While it is possible that this protection is due to subtle differences in brain temperature during early reperfusion, we speculate that additional mechanisms may be involved. Our findings add to the growing understanding of brain-body cross

  1. Rebound hyperthermia follows ethanol-induced hypothermia in rats.

    PubMed

    Gallaher, E J; Egner, D A

    1987-01-01

    We have recently described a telemetry/microcomputer system to monitor core temperatures in rats. We implant a miniature transmitter (Mini-mitter) into the peritoneal cavity of the rat, allowing us to obtain temperatures around the clock without handling the animals or disturbing the light-dark cycle. In the present study we describe the temperature effects of ethanol doses ranging from 2 to 6 g/kg. Baseline temperatures were collected for 2 days before drug was administered. Subsequent computer analysis then allowed us to compare experimental results in each animal with its own baseline temperature to allow for individual and circadian temperature differences. In preliminary studies we observed the well-known dose-dependent hypothermic effect of ethanol. However, by observing animals continually over 4 days we also observed a period of rebound hyperthermia beginning at about the time of complete ethanol elimination and persisting for several days. During this period daytime temperatures remained at the normally high night-time level. This may be evidence of a mild abstinence syndrome, or alternatively, may be due to a disruption of the normal circadian temperature rhythm. PMID:3103157

  2. Ca++ induced hypothermia in a hibernator /Citellus beechyi/

    NASA Technical Reports Server (NTRS)

    Hanegan, J. L.; Williams, B. A.

    1975-01-01

    Results of perfusion of excess Ca++ and Na+ into the hypothalamus of the hibernating ground squirrel Citellus beechyi are presented. The significant finding is that perfused excess Ca++ causes a reduction in core temperature when ambient temperature is low (12 C). Ca++ also causes a rise in rectal temperature at high ambient temperature (33 C). Thus hypothalamic Ca++ perfusion apparently causes a nonspecific depression of thermoregulatory control.

  3. The importance of cold-reactive autoantibodies in an asphyxiated infant before therapeutic hypothermia.

    PubMed

    Beken, Serdar; Altuntaş, Nilgün; Koç, Esin; Yenicesu, Idil; Ergenekon, Ebru; Hirfanoğlu, Ibrahim Murat; Onal, Esra; Türkyilmaz, Canan; Atalay, Yildiz

    2013-11-01

    Perinatal asphyxia is an important cause of neonatal morbidity and mortality. Hypothermia is an effective treatment of neonatal hypoxic-ischemic encephalopathy in infants. Cold agglutination is a primary or acquired autoimmune disease that involves autoantibodies that lead to hemagglutination at low temperatures lower than that of the body. In this case the importance of cold agglutinins during therapeutic hypothermia is presented. PMID:23271311

  4. Hypothermia-related deaths--Wisconsin, 2014, and United States, 2003-2013.

    PubMed

    Meiman, Jon; Anderson, Henry; Tomasallo, Carrie

    2015-02-20

    Hypothermia is defined as a core body temperature of <95°F (<35°C) and is caused by environmental exposure, drug intoxication, or metabolic or nervous system dysfunction. Exposure to cold is a leading cause of weather-related mortality and is responsible for approximately twice the number of deaths annually as exposure to heat in the United States. To understand the risk factors for hypothermia-related death and improve prevention efforts, during January 1-April 30, 2014, a period of record low temperatures, the Wisconsin Division of Public Health began active surveillance for hypothermia. Suspected hypothermia-related deaths were reported by coroners or medical examiners and identified in death records. Hypothermia was confirmed as the cause of death by review of death investigation narratives. This report describes three selected cases of hypothermia-related deaths in Wisconsin and summarizes characteristics of all cases that occurred in the state during the period of active surveillance. A summary of hypothermia-related deaths for the United States during 2003-2013 also is presented for comparison and to assess national mortality trends. Hypothermia continues to be an important cause of weather-related death. Key risk factors include drug intoxication, mental illness, and social isolation. State and local health agencies might need to focus outreach on vulnerable populations and target interventions for groups at highest risk for death. PMID:25695318

  5. Platelet Function During Hypothermia in Experimental Mock Circulation.

    PubMed

    Van Poucke, Sven; Stevens, Kris; Kicken, Cécile; Simons, Antoine; Marcus, Abraham; Lancé, Marcus

    2016-03-01

    Alterations in platelet function are a common finding in surgical procedures involving cardiopulmonary bypass and hypothermia. Although the combined impact of hypothermia and artificial circulation on platelets has been studied before, the ultimate strategy to safely minimize the risk for bleeding and thrombosis is yet unknown. The aim of this study was to evaluate the use of a mock circulation loop to study the impact of hypothermia for platelet-related hemostatic changes. Venous blood was collected from healthy adult humans (n = 3). Closed mock circulation loops were assembled, each consisting of a centrifugal pump, an oxygenator with integrated heat exchanger, and a hardshell venous reservoir. The experiment started with the mock circulation temperature set at 37°C (T0 [0 h]). Cooling was then initiated at T1 (+2 h), where temperature was adjusted from 37°C to 32°C. Hypothermia was maintained from T2 (+4 h) to T3 (+28 h). From that point in time, rewarming from 32°C to 37°C was initiated with similar speed as cooling. From time point T4 (+30 h), normothermia (37°C) was maintained until the experiment ended at T5 (+32 h). Blood samples were analyzed in standard hematological tests: light transmission aggregometry (LTA) (arachidonic acid [AA], adenosine diphosphate [ADP], collagen [COL], thrombin-receptor-activating-peptide-14 [TRAP]), multiple electrode aggregometry (MEA) (AA, ADP, COL, TRAP), and rotational thromboelastometry (ROTEM) (EXTEM, FIBTEM, PLTEM). Hemoglobin, hematocrit, and platelet count decrease more substantially during temperature drop (37-32°C) than during hypothermia maintenance. Hb and Hct continue to follow this trend during active rewarming (32-37°C). PC increase from the moment active rewarming was initiated. None of the values return to the initial values. LTA values demonstrate a similar decrease in aggregation after stimulation with the platelet agonists between the start of the mock circulation and the start of cooling. Except

  6. Neonatal Encephalopathy: Update on Therapeutic Hypothermia and Other Novel Therapeutics.

    PubMed

    McAdams, Ryan M; Juul, Sandra E

    2016-09-01

    Neonatal encephalopathy (NE) is a major cause of neonatal mortality and morbidity. Therapeutic hypothermia (TH) is standard treatment for newborns at 36 weeks of gestation or greater with intrapartum hypoxia-related NE. Term and late preterm infants with moderate to severe encephalopathy show improved survival and neurodevelopmental outcomes at 18 months of age after TH. TH can increase survival without increasing major disability, rates of an IQ less than 70, or cerebral palsy. Neonates with severe NE remain at risk of death or severe neurodevelopmental impairment. This review discusses the evidence supporting TH for term or near term neonates with NE. PMID:27524449

  7. Protein SUMOylation is massively increased in hibernation torpor and is critical for the cytoprotection provided by ischemic preconditioning and hypothermia in SHSY5Y cells

    PubMed Central

    Lee, Yang-ja; Miyake, Shin-ichi; Wakita, Hideaki; McMullen, David C; Azuma, Yoshiaki; Auh, Sungyoung; Hallenbeck, John M

    2008-01-01

    Hibernation torpor provides an excellent natural model of tolerance to profound reductions in blood flow to the brain and other organs. Here, we report that during torpor of 13-lined ground squirrels, massive SUMOylation occurs in the brain, liver, and kidney. The level of small ubiquitin-related modifier (SUMO) conjugation coincides with the expression level of Ubc9, the SUMO specific E2-conjugating enzyme. Hypothermia alone also increased SUMO conjugation, but not as markedly as hibernation torpor. Increased SUMO conjugation (induced by Ubc9 overexpression, ischemic preconditioning (PC)±hypothermia) was necessary and sufficient for tolerance of SHSY5Y neuroblastoma cells to oxygen/glucose deprivation (OGD) (‘in vitro ischemia’); decreased SUMO conjugation (induced by a dominant-negative Ubc9) severely reduced tolerance to OGD in these cells. These data indicate that post-translational modification of proteins by SUMOylation is a prominent feature of hibernation torpor and is critical for cytoprotection by ischemic PC± hypothermia in SHSY5Y cells subjected to OGD. PMID:16955077

  8. Lower Incidence of Seizure among Neonates Treated with Therapeutic Hypothermia

    PubMed Central

    Orbach, Sharon A; Bonifacio, Sonia L; Kuzniewicz, Michael; Glass, Hannah C

    2013-01-01

    Animal studies suggest that hypothermia decreases seizure burden, while limited human data are inconclusive. This retrospective cohort study examines the relationship between therapeutic hypothermia and seizure in neonates with hypoxic-ischemic encephalopathy. Our center admitted 224 neonates from July 2004 to December 2011 who met institutional cooling criteria. Seventy-three neonates were born during the pre-cooling era, prior to November 2007, and 151 were born during the cooling era. Among neonates with moderate encephalopathy, the incidence of seizure in cooled infants was less than half the incidence in those not cooled (26% cooling versus 61% pre-cooling era; RR=0.43, 95% CI 0.30 to 0.61). Among neonates with severe encephalopathy, there was no difference in the incidence (83% versus 87%; RR=1.05, 95% CI 0.78 to 1.39). These results support animal data and suggest a mechanism by which neonates with moderate encephalopathy may benefit more from cooling than neonates with severe encephalopathy. PMID:24334344

  9. Achilles Tendon Reflex in Accidental Hypothermia and Hypothermic Myxoedema

    PubMed Central

    Maclean, D.; Taig, D. R.; Emslie-Smith, D.

    1973-01-01

    The photomotogram (P.M.G.) of the Achilles tendon reflex was studied in 26 patients with hypothermia (rectal temperature 33·3°C or less), 10 of whom also had myxoedema (serum protein bound iodine 2·8 μg/100 ml or less). No reflex could be elicited in eight (31%) of these patients, including three of those with myxoedema. Hypothermia increases both the contraction and the relaxation times of the reflex, the relaxation phase being particularly prolonged in those with myxoedema. In those patients from whom the reflex was elicited the ratio of the contraction time to the “half-relaxation time” in the P.M.G. was less than unity in six of the seven with myxoedema, and considerably greater than unity in eight of the 11 (73%) who were euthyroid. Thus, analysis of the Achilles tendon reflex P.M.G. correctly predicted the thyroid status in 14 of the 18 hypothermic patients in whom the Achilles tendon reflex was present (78%). The wider use of this rapid test of thyroid function would allow a more rational use of thyroid hormones in hypothermic patients and so lead to a better assessment of their value. PMID:4121692

  10. Catecholamines and free fatty acids in plasma of patients undergoing cardiac operations with hypothermia and bypass.

    PubMed Central

    Hirvonen, J; Huttunen, P; Nuutinen, L; Pekkarinen, A

    1978-01-01

    Plasma concentrations of adrenaline, noradrenaline, and free fatty acids were measured at different stages of cardiac operations in which hypothermia and bypass were used. The rise of adrenaline, noradrenaline, and free fatty acid concentrations in plasma is consistent with the concept that these are important compounds in stress situations such as hypothermia and surgical operations. There is a more marked release of adrenaline and it may be a more specific hormone in response to hypothermia and bypass than is noradrenaline in man. PMID:711903

  11. Prehospital therapeutic hypothermia after cardiac arrest--from current concepts to a future standard.

    PubMed

    Kämäräinen, Antti; Hoppu, Sanna; Silfvast, Tom; Virkkunen, Ilkka

    2009-01-01

    Therapeutic hypothermia has been shown to improve survival and neurological outcome after prehospital cardiac arrest. Existing experimental and clinical evidence supports the notion that delayed cooling results in lesser benefit compared to early induction of mild hypothermia soon after return of spontaneous circulation. Therefore a practical approach would be to initiate cooling already in the prehospital setting. The purpose of this review was to evaluate current clinical studies on prehospital induction of mild hypothermia after cardiac arrest. Most reported studies present data on cooling rates, safety and feasibility of different methods, but are inconclusive as regarding to outcome effects. PMID:19821967

  12. Prehospital therapeutic hypothermia after cardiac arrest - from current concepts to a future standard

    PubMed Central

    Kämäräinen, Antti; Hoppu, Sanna; Silfvast, Tom; Virkkunen, Ilkka

    2009-01-01

    Therapeutic hypothermia has been shown to improve survival and neurological outcome after prehospital cardiac arrest. Existing experimental and clinical evidence supports the notion that delayed cooling results in lesser benefit compared to early induction of mild hypothermia soon after return of spontaneous circulation. Therefore a practical approach would be to initiate cooling already in the prehospital setting. The purpose of this review was to evaluate current clinical studies on prehospital induction of mild hypothermia after cardiac arrest. Most reported studies present data on cooling rates, safety and feasibility of different methods, but are inconclusive as regarding to outcome effects. PMID:19821967

  13. Induction of therapeutic hypothermia by pharmacological modulation of temperature-sensitive TRP channels: theoretical framework and practical considerations

    PubMed Central

    Feketa, Viktor V; Marrelli, Sean P

    2015-01-01

    Therapeutic hypothermia has emerged as a remarkably effective method of neuroprotection from ischemia and is being increasingly used in clinics. Accordingly, it is also a subject of considerable attention from a basic scientific research perspective. One of the fundamental problems, with which current studies are concerned, is the optimal method of inducing hypothermia. This review seeks to provide a broad theoretical framework for approaching this problem, and to discuss how a novel promising strategy of pharmacological modulation of the thermosensitive ion channels fits into this framework. Various physical, anatomical, physiological and molecular aspects of thermoregulation, which provide the foundation for this text, have been comprehensively reviewed and will not be discussed exhaustively here. Instead, the first part of the current review, which may be helpful for a broader readership outside of thermoregulation research, will build on this existing knowledge to outline possible opportunities and research directions aimed at controlling body temperature. The second part, aimed at a more specialist audience, will highlight the conceptual advantages and practical limitations of novel molecular agents targeting thermosensitive Transient Receptor Potential (TRP) channels in achieving this goal. Two particularly promising members of this channel family, namely TRP melastatin 8 (TRPM8) and TRP vanilloid 1 (TRPV1), will be discussed in greater detail. PMID:27227027

  14. Effects of Sex and Mild Intrainsult Hypothermia on Neuropathology and Neural Reorganization following Neonatal Hypoxic Ischemic Brain Injury in Rats

    PubMed Central

    Smith, Amanda L.; Rosenkrantz, Ted S.; Fitch, R. Holly

    2016-01-01

    Hypoxia ischemia (HI) is a recognized risk factor among late-preterm infants, with HI events leading to varied neuropathology and cognitive/behavioral deficits. Studies suggest a sex difference in the incidence of HI and in the severity of subsequent behavioral deficits (with better outcomes in females). Mechanisms of a female advantage remain unknown but could involve sex-specific patterns of compensation to injury. Neuroprotective hypothermia is also used to ameliorate HI damage and attenuate behavioral deficits. Though currently prescribed only for HI in term infants, cooling has potential intrainsult applications to high-risk late-preterm infants as well. To address this important clinical issue, we conducted a study using male and female rats with a postnatal (P) day 7 HI injury induced under normothermic and hypothermic conditions. The current study reports patterns of neuropathology evident in postmortem tissue. Results showed a potent benefit of intrainsult hypothermia that was comparable for both sexes. Findings also show surprisingly different patterns of compensation in the contralateral hemisphere, with increases in hippocampal thickness in HI females contrasting reduced thickness in HI males. Findings provide a framework for future research to compare and contrast mechanisms of neuroprotection and postinjury plasticity in both sexes following a late-preterm HI insult. PMID:27042359

  15. Hypothermia for Increased Intracranial Pressure: Is It Dead?

    PubMed

    Lazaridis, Christos; Robertson, Claudia S

    2016-09-01

    Mild to moderate therapeutic hypothermia (HT) has been used to alleviate intracranial hypertension in traumatic brain injury (TBI). Its main contribution is thought to be via reduction in cerebral metabolic requirement leading both to favorable oxygen/metabolic delivery-demand ratios as well as a reduction of cerebral blood volume resulting in decreased ICP. Nevertheless, HT is a clinically complex, labor-intensive procedure with numerous potential adverse effects. Furthermore, randomized controlled trials suggest either no effect or harm. These facts challenge the role of HT in TBI. We address this challenge by posing three questions that relate to the overarching value of controlling ICP, the effectiveness of HT in reducing ICP, and the benefit-risk ratio of the intervention. We conclude that HT should not be used as an "early" intervention unless as a part of a clinical trial, although it may still have a role in patients with refractory intracranial hypertension. PMID:27443645

  16. Insomnia Caused by Serotonin Depletion is Due to Hypothermia

    PubMed Central

    Murray, Nicholas M.; Buchanan, Gordon F.; Richerson, George B.

    2015-01-01

    Study Objective: Serotonin (5-hydroxytryptamine, 5-HT) neurons are now thought to promote wakefulness. Early experiments using the tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA) had led to the opposite conclusion, that 5-HT causes sleep, but those studies were subsequently contradicted by electrophysiological and behavioral data. Here we tested the hypothesis that the difference in conclusions was due to failure of early PCPA experiments to control for the recently recognized role of 5-HT in thermoregulation. Design: Adult male C57BL/6N mice were treated with PCPA (800 mg/kg intraperitoneally for 5 d; n = 15) or saline (n = 15), and housed at 20°C (normal room temperature) or at 33°C (thermoneutral for mice) for 24 h. In a separate set of experiments, mice were exposed to 4°C for 4 h to characterize their ability to thermoregulate. Measurements and Results: PCPA treatment reduced brain 5-HT to less than 12% of that of controls. PCPA-treated mice housed at 20°C spent significantly more time awake than controls. However, core body temperature decreased from 36.5°C to 35.1°C. When housed at 33°C, body temperature remained normal, and total sleep duration, sleep architecture, and time in each vigilance state were the same as controls. When challenged with 4°C, PCPA-treated mice experienced a precipitous drop in body temperature, whereas control mice maintained a normal body temperature. Conclusions: These results indicate that early experiments using para-chlorophenylalanine that led to the conclusion that 5-hydroxytryptamine (5-HT) causes sleep were likely confounded by hypothermia. Temperature controls should be considered in experiments using 5-HT depletion. Citation: Murray NM, Buchanan GF, Richerson GB. Insomnia caused by serotonin depletion is due to hypothermia. SLEEP 2015;38(12):1985–1993. PMID:26194567

  17. Biomarkers of Brain Injury in Neonatal Encephalopathy Treated with Hypothermia

    PubMed Central

    Massaro, An N.; Chang, Taeun; Kadom, Nadja; Tsuchida, Tammy; Scafidi, Joseph; Glass, Penny; McCarter, Robert; Baumgart, Stephen; Vezina, Gilbert; Nelson, Karin B.

    2012-01-01

    Objective To determine if early serum S100B and neuron-specific enolase (NSE) levels are associated with neuroradiographic and clinical evidence of brain injury in newborns with encephalopathy. Study design Patients who received therapeutic whole-body hypothermia were prospectively enrolled in this observational study. Serum specimens were collected at 0, 12, 24, and 72 hours of cooling. S100B and NSE levels were measured by enzyme linked immunosorbent assay. Magnetic resonance imaging was performed in surviving infants at 7–10 days of life. Standardized neurologic examination was performed by a child neurologist at 14 days of life. Multiple linear regression analyses were performed to evaluate the association between S100B and NSE levels and unfavorable outcome (death or severe magnetic resonance imaging injury/significant neurologic deficit). Cutoff values were determined by receiver operating curve analysis. Results Newborns with moderate to severe encephalopathy were enrolled (n = 75). Median pH at presentation was 6.9 (range, 6.5–7.35), and median Apgar scores of 1 at 1 minute, 3 at 5 minutes, and 5 at 10 minutes. NSE and S100B levels were higher in patients with unfavorable outcomes across all time points. These results remained statistically significant after controlling for covariables, including encephalopathy grade at presentation, Apgar score at 5 minutes of life, initial pH, and clinical seizures. Conclusion Elevated serum S100B and NSE levels measured during hypothermia were associated with neuroradiographic and clinical evidence of brain injury in encephalopathic newborns. These brain-specific proteins may be useful immediate biomarkers of cerebral injury severity. PMID:22494878

  18. How does mild hypothermia affect monoclonal antibody glycosylation?

    PubMed

    Sou, Si Nga; Sellick, Christopher; Lee, Ken; Mason, Alison; Kyriakopoulos, Sarantos; Polizzi, Karen M; Kontoravdi, Cleo

    2015-06-01

    The application of mild hypothermic conditions to cell culture is a routine industrial practice used to improve recombinant protein production. However, a thorough understanding of the regulation of dynamic cellular processes at lower temperatures is necessary to enhance bioprocess design and optimization. In this study, we investigated the impact of mild hypothermia on protein glycosylation. Chinese hamster ovary (CHO) cells expressing a monoclonal antibody (mAb) were cultured at 36.5°C and with a temperature shift to 32°C during late exponential/early stationary phase. Experimental results showed higher cell viability with decreased metabolic rates. The specific antibody productivity increased by 25% at 32°C and was accompanied by a reduction in intracellular nucleotide sugar donor (NSD) concentrations and a decreased proportion of the more processed glycan structures on the mAb constant region. To better understand CHO cell metabolism at 32°C, flux balance analysis (FBA) was carried out and constrained with exometabolite data from stationary phase of cultures with or without a temperature shift. Estimated fluxomes suggested reduced fluxes of carbon species towards nucleotide and NSD synthesis and more energy was used for product formation. Expression of the glycosyltransferases that are responsible for N-linked glycan branching and elongation were significantly lower at 32°C. As a result of mild hypothermia, mAb glycosylation was shown to be affected by both NSD availability and glycosyltransferase expression. The combined experimental/FBA approach generated insight as to how product glycosylation can be impacted by changes in culture temperature. Better feeding strategies can be developed based on the understanding of the metabolic flux distribution. PMID:25545631

  19. Angiogenesis Dysregulation in Term Asphyxiated Newborns Treated with Hypothermia

    PubMed Central

    Shaikh, Henna; Boudes, Elodie; Khoja, Zehra; Shevell, Michael; Wintermark, Pia

    2015-01-01

    Background Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns. Objective This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns. Design/Methods Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns. Results Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns. Conclusions These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery. PMID:25996847

  20. Heat and cold acclimation in helium-cold hypothermia in the hamster.

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.

    1972-01-01

    A study was made of the effects of acclimation of hamsters to high (34-35 C) and low (4-5 C) temperatures for periods up to 6 weeks on the induction of hypothermia in hamsters. Hypothermia was achieved by exposing hamsters to a helox mixture of 80% helium and 20% oxygen at 0 C. Hypothermic induction was most rapid (2-3 hr) in heat-acclimated hamsters and slowest (6-12 hr) in cold-acclimated hamsters. The induction period was intermediate (5-8 hr) in room temperature nonacclimated animals (controls). Survival time in hypothermia was relatable to previous temperature acclimations. The hypothesis that thermogenesis in cold-acclimated hamsters would accentuate resistance to induction of hypothermia was substantiated.

  1. Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway

    PubMed Central

    2014-01-01

    Background Therapeutic hypothermia is a treatment modality that is increasingly used to improve clinical neurological outcomes for ischemia-reperfusion injury-mediated diseases. Antibody-initiated classical complement pathway activation has been shown to contribute to ischemia-reperfusion injury in multiple disease processes. However, how therapeutic hypothermia affects complement activation is unknown. Our goal was to measure the independent effect of temperature on complement activation, and more specifically, examine the relationship between clinical hypothermia temperatures (31–33°C), and complement activation. Methods Antibody-sensitized erythrocytes were used to assay complement activation at temperatures ranging from 0-41°C. Individual complement pathway components were assayed by ELISA, Western blot, and quantitative dot blot. Peptide Inhibitor of complement C1 (PIC1) was used to specifically inhibit activation of C1. Results Antibody-initiated complement activation resulting in eukaryotic cell lysis was increased by 2-fold at 31°C compared with 37°C. Antibody-initiated complement activation in human serum increased as temperature decreased from 37°C until dramatically decreasing at 13°C. Quantitation of individual complement components showed significantly increased activation of C4, C3, and C5 at clinical hypothermia temperatures. In contrast, C1s activation by heat-aggregated IgG decreased at therapeutic hypothermia temperatures consistent with decreased enzymatic activity at lower temperatures. However, C1q binding to antibody-coated erythrocytes increased at lower temperatures, suggesting that increased classical complement pathway activation is mediated by increased C1 binding at therapeutic hypothermia temperatures. PIC1 inhibited hypothermia-enhanced complement-mediated cell lysis at 31°C by up to 60% (P = 0.001) in a dose dependent manner. Conclusions In summary, therapeutic hypothermia temperatures increased antibody

  2. Case of Recurrent Ventricular Fibrillations with Osborn Wave Developed during Therapeutic Hypothermia.

    PubMed

    Kim, Chang-Yeon; Bae, Myung Hwan; Kim, Nam Kyun; Yang, Young Ae; Kim, Kyu Yeun; Lee, Jang Hoon; Eun, Jung Su; Cho, Yongkeun

    2015-01-01

    Therapeutic hypothermia (TH) has been used to protect neurological functions in cardiac arrest patient. Although Osborn wave is not pathognomonic of hypothermia, it is a well-known electrocardiogram finding of hypothermic patients. The cellular and ionic mechanisms of the Osborn wave have been suggested, and its relationship to tachyarrhythmias, such as ventricular tachycardia and ventricular fibrillation, is being explored. This case highlights the arrhythmogenic potential of Osborn wave and individual difference in response of TH. PMID:25653709

  3. Is hypothermia in the victim of major trauma protective or harmful? A randomized, prospective study.

    PubMed Central

    Gentilello, L M; Jurkovich, G J; Stark, M S; Hassantash, S A; O'Keefe, G E

    1997-01-01

    OBJECTIVE: The purpose of this randomized, prospective clinical trial was to determine whether hypothermia during resuscitation is protective or harmful to critically injured trauma patients. SUMMARY BACKGROUND DATA: Hypothermia has both protective and harmful clinical effects. Retrospective studies show higher mortality in patients with hypothermia; however, hypothermia is more common in more severely injured patients, which makes it difficult to determine whether hypothermia contributes to mortality independently of injury severity. There are no randomized, prospective treatment studies to assess hypothermia's impact as an independent variable. METHODS: Fifty-seven hypothermic (T < or = 34.5 C), critically injured patients requiring a pulmonary artery catheter were randomized to a rapid rewarming protocol using continuous arteriovenous rewarming (CAVR) or to a standard rewarming (SR) control group. The primary outcome of interest was first 24-hour blood product and fluid resuscitation requirements. Other comparative analyses included coagulation assays, hemodynamic and oxygen transport measurements, length of stay, and mortality. RESULTS: The two groups were well matched for demographic and injury severity characteristics. CAVR rewarmed significantly faster than did SR (p < 0.01), producing two groups with different amounts of hypothermia exposure. The patients who underwent CAVR required less fluid during resuscitation to the same hemodynamic goals (24,702 mL vs. 32,540 mL, p = 0.05) and were significantly more likely to rewarm (p = 0.002). Only 2 (7%) of 29 patients who underwent CAVR failed to warm to 36 C and both died, whereas 12 (43%) of 28 patients who underwent SR failed to reach 36 C, and all 12 died. Patients who underwent CAVR had significantly less early mortality (p = 0.047). CONCLUSION: Hypothermia increases fluid requirements and independently increases acute mortality after major trauma. PMID:9351712

  4. SU-C-213-07: Fabrication and Testing of a 3D-Printed Small Animal Rectal Cooling Device to Evaluate Local Hypothermia as a Radioprotector During Prostate SBRT

    SciTech Connect

    Hrycushko, B; Chopra, R; Futch, C; Bing, C; Wodzak, M; Stojadinovic, S; Jiang, S; Medin, P

    2015-06-15

    Purpose: The protective effects of induced or even accidental hypothermia on the human body are widespread with several medical uses currently under active research. In vitro experiments using human cell lines have shown hypothermia provides a radioprotective effect that becomes more pronounced at large, single-fraction doses common to SBRT treatments. Relevant to prostate SBRT, this work details the fabrication and testing of a 3D-printed cooling device to facilitate the investigation of the radioprotective effect of local hypothermia on the rat rectum. Methods: A 3cm long, two-channel rectal cooling device was designed in SOLIDWORKS CAD for 3D printing. The water intake nozzle is connected to a 1mm diameter brass pipe from which water flows and circulates back around to the exit nozzle. Both nozzles are connected by plastic tubing to a water chiller pump. Following leak-proof testing, fiber optic temperature probes were used to evaluate the temperature over time when placed adjacent to the cooling device within a rat rectum. MRI thermometry characterized the relative temperature distribution in concentric ROIs surrounding the probe. CBCT images from a small-animal irradiator were evaluated for imaging artifacts which could affect Monte Carlo dose calculations during treatment planning. Results: The rectal temperature adjacent to the cooling device decreased from body temperature (37°C) to 15°C in 10–20 minutes from device insertion. Rectal temperature was maintained at 15±3°C during active cooling. MRI thermometry tests revealed a steep temperature gradient with increasing distance from the cooling device, with the desired temperature range maintained within the surrounding few millimeters. Conclusion: A 3D printed rectal cooling device was fabricated for the purpose of inducing local hypothermia in rat rectums. Rectal cooling capabilities were characterized in-vivo to facilitate an investigation of the radioprotective effect of hypothermia for late rectal

  5. Effect of Temperature on Thromboelastography (TEG) and Implications for Clinical Use in Neonates Undergoing Therapeutic Hypothermia

    PubMed Central

    Forman, Katie R.; Wong, Edward; Gallagher, Meanavy; McCarter, Robert; Luban, Naomi L.C.; Massaro, An N.

    2014-01-01

    Background Encephalopathic neonates undergoing therapeutic hypothermia have increased risk for coagulopathy secondary to perinatal asphyxia and effects of cooling on the coagulation enzyme cascade. Thromboelastography (TEG) allows for a comprehensive assessment of coagulation that can be regulated for temperature. TEG has not been previously evaluated in newborns undergoing hypothermia treatment. Methods Encephalopathic neonates treated with systemic hypothermia were enrolled in this prospective observational study. Daily blood specimens were collected for standard coagulation tests and platelet counts during hypothermia and after rewarming. Concurrent TEG assays were performed at 33.5°C and 37.0°C for comparison. Results A total of 48 paired TEGs from 24 subjects were performed. Mean (± SD) birthweight was 3.2±0.7 Kg, gestational age 38.4±1.4 weeks, and 40% were male. TEG results differed significantly between assays performed at 37.0°C versus 33.5°C, indicating more impaired coagulation at 33.5°C. TEG parameters K, α, MA and CI were significantly associated with clinical bleeding (p<0.05). These remained significant (except for MA) after controlling for transfusion therapy. Conclusions TEG results are affected by temperature, consistent with the known association of hypothermia with coagulopathy. Several TEG parameters are predictive of clinical bleeding in newborns undergoing hypothermia. Selected cutpoints to predict bleeding risk are temperature dependent. PMID:24522100

  6. Dantrolene enhances the protective effect of hypothermia on cerebral cortex neurons

    PubMed Central

    Xu, Sui-yi; Hu, Feng-yun; Ren, Li-jie; Chen, Lei; Zhou, Zhu-qing; Zhang, Xie-jun; Li, Wei-ping

    2015-01-01

    Therapeutic hypothermia is the most promising non-pharmacological neuroprotective strategy against ischemic injury. However, shivering is the most common adverse reaction. Many studies have shown that dantrolene is neuroprotective in in vitro and in vivo ischemic injury models. In addition to its neuroprotective effect, dantrolene neutralizes the adverse reaction of hypothermia. Dantrolene may be an effective adjunctive therapy to enhance the neuroprotection of hypothermia in treating ischemic stroke. Cortical neurons isolated from rat fetuses were exposed to 90 minutes of oxygen-glucose deprivation followed by reoxygenation. Neurons were treated with 40 μM dantrolene, hypothermia (at 33°C), or the combination of both for 12 hours. Results revealed that the combination of dantrolene and hypothermia increased neuronal survival and the mitochondrial membrane potential, and reduced intracellular active oxygen cytoplasmic histone-associated DNA fragmentation, and apoptosis. Furthermore, improvements in cell morphology were observed. The combined treatment enhanced these responses compared with either treatment alone. These findings indicate that dantrolene may be used as an effective adjunctive therapy to enhance the neuroprotective effects of hypothermia in ischemic stroke. PMID:26487856

  7. Heart Rate and Arterial Pressure Changes during Whole-Body Deep Hypothermia.

    PubMed

    Cavallaro, Giacomo; Filippi, Luca; Raffaeli, Genny; Cristofori, Gloria; Schena, Federico; Agazzani, Elisa; Amodeo, Ilaria; Griggio, Alice; Boccacci, Simona; Fiorini, Patrizio; Mosca, Fabio

    2013-01-01

    Whole-body deep hypothermia (DH) could be a new therapeutic strategy for asphyxiated newborn. This retrospective study describes how DH modified the heart rate and arterial blood pressure if compared to mild hypothermia (MH). Fourteen in DH and 17 in MH were cooled within the first six hours of life and for the following 72 hours. Hypothermia criteria were gestational age ≥36 weeks; birth weight ≥1800 g; clinical signs of moderate/severe hypoxic-ischemic encephalopathy. Rewarming was obtained in the following 6-12 hours (0.5°C/h) after cooling. Heart rates were the same between the two groups; there was statistically significant difference at the beginning of hypothermia and during rewarming. Three babies in the DH group and 2 in the MH group showed HR < 80 bpm and QTc > 520 ms. Infant submitted to deep hypothermia had not bradycardia or Qtc elongation before cooling and after rewarming. Blood pressure was significantly lower in DH compared to MH during the cooling, and peculiar was the hypotension during rewarming in DH group. Conclusion. The deeper hypothermia is a safe and feasible, only if it is performed by a well-trained team. DH should only be associated with a clinical trial and prospective randomized trials to validate its use. PMID:23691350

  8. Heart Rate and Arterial Pressure Changes during Whole-Body Deep Hypothermia

    PubMed Central

    Cavallaro, Giacomo; Filippi, Luca; Raffaeli, Genny; Cristofori, Gloria; Schena, Federico; Agazzani, Elisa; Amodeo, Ilaria; Griggio, Alice; Boccacci, Simona; Fiorini, Patrizio; Mosca, Fabio

    2013-01-01

    Whole-body deep hypothermia (DH) could be a new therapeutic strategy for asphyxiated newborn. This retrospective study describes how DH modified the heart rate and arterial blood pressure if compared to mild hypothermia (MH). Fourteen in DH and 17 in MH were cooled within the first six hours of life and for the following 72 hours. Hypothermia criteria were gestational age ≥36 weeks; birth weight ≥1800 g; clinical signs of moderate/severe hypoxic-ischemic encephalopathy. Rewarming was obtained in the following 6–12 hours (0.5°C/h) after cooling. Heart rates were the same between the two groups; there was statistically significant difference at the beginning of hypothermia and during rewarming. Three babies in the DH group and 2 in the MH group showed HR < 80 bpm and QTc > 520 ms. Infant submitted to deep hypothermia had not bradycardia or Qtc elongation before cooling and after rewarming. Blood pressure was significantly lower in DH compared to MH during the cooling, and peculiar was the hypotension during rewarming in DH group. Conclusion. The deeper hypothermia is a safe and feasible, only if it is performed by a well-trained team. DH should only be associated with a clinical trial and prospective randomized trials to validate its use. PMID:23691350

  9. The Practice of Therapeutic Hypothermia after Cardiac Arrest in France: A National Survey

    PubMed Central

    Orban, Jean-Christophe; Cattet, Florian; Lefrant, Jean-Yves; Leone, Marc; Jaber, Samir; Constantin, Jean-Michel; Allaouchiche, Bernard; Ichai, Carole

    2012-01-01

    Aims Cardiac arrest is a major health concern worldwide accounting for 375,000 cases per year in Europe with a survival rate of <10%. Therapeutic hypothermia has been shown to improve patients’ neurological outcome and is recommended by scientific societies. Despite these guidelines, different surveys report a heterogeneous application of this treatment. The aim of the present study was to evaluate the clinical practice of therapeutic hypothermia in cardiac arrest patients. Methods This self-declarative web based survey was proposed to all registered French adult intensive care units (ICUs) (n = 357). Paediatrics and neurosurgery ICUs were excluded. The different questions addressed the structure, the practical modalities of therapeutic hypothermia and the use of prognostic factors in patients admitted after cardiac arrest. Results One hundred and thirty-two out of 357 ICUs (37%) answered the questionnaire. Adherence to recommendations regarding the targeted temperature and hypothermia duration were 98% and 94% respectively. Both guidelines were followed in 92% ICUs. During therapeutic hypothermia, sedative drugs were given in 99% ICUs, mostly midazolam (77%) and sufentanil (59%). Neuromuscular blocking agents (NMBA) were used in 97% ICUs, mainly cisatracurium (77%). Numerous prognostic factors were used after cardiac arrest such as clinical factors (95%), biomarkers (53%), electroencephalography (78%) and evoked potentials (35%). Conclusions In France, adherence to recommendations for therapeutic hypothermia after cardiac arrest is higher than those previously reported in other countries. Numerous prognostic factors are widely used even if their reliability remains controversial. PMID:23049783

  10. Survey on Hypothermia and Hyperthermia in Poisoned Patients in a Unique Referral Hospital, Tehran, Iran

    PubMed Central

    Mozafari, Naser; Talaie, Haleh; Shoaei, Simin Dokht; Hashemian, Morteza; Mahdavinejad, Arezou

    2016-01-01

    975 IU/L were recorded in 57.7% and 13.2% of subjects, respectively. Conclusions Body temperature changes in human poisonings are a matter in need of special attention. A literature review did not reveal any controversy over hypothermia, but poisoning cases exhibit a variety of patterns of fever and hyperthermia. If there are no limits to the diagnosis of fever and hyperthermia, all cases with a poor prognosis which fail to respond to treatment could be categorized as drug-induced hyperthermia. Therefore, a different approach is needed for poisoning cases. PMID:27275403

  11. Good neurologic recovery after cardiac arrest using hypothermia through continuous renal replacement therapy.

    PubMed

    Ma, Yu-jie; Ning, Bo; Cao, Wei-hong; Liu, Tao; Liu, Lei

    2013-12-01

    Therapeutic hypothermia (TH) is becoming a standard of care to mitigate neurologic injury in cardiac arrest survivors. Several cooling methods are available for use in TH. For maintaining a target temperature, intravascular cooling is superior to, more efficacious than, and safer than surface cooling methods. The use of an intravenous cooling catheter is independently associated with a higher odds ratio for survival. However, many techniques use commercially developed equipment that is expensive to purchase and use. The application and popularization of the intravascular cooling method have been difficult. In patients with pulmonary edema or cardiac insufficiency, liquid is restricted, so intravascular cooling systems cannot be used. Studies have shown abnormalities mimicking the immunologic and coagulation disorders observed in severe sepsis. Continuous renal replacement therapy has been widely used in the intensive care unit to improve clinical parameters and survival in patients with multiple-organ dysfunction of septic origin. Continuous renal replacement therapy can also be used as another type of core cooling method. We used continuous renal replacement therapy as a cooling method to induce TH in a patient who had a cardiac arrest, and the patient regained consciousness 52 hours later. PMID:23953774

  12. Protective effect of hypothermia on brain potassium homeostasis during repetitive anoxia in Drosophila melanogaster.

    PubMed

    Rodríguez, Esteban C; Robertson, R Meldrum

    2012-12-01

    Oxygen deprivation in nervous tissue depolarizes cell membranes, increasing extracellular potassium concentration ([K(+)](o)). Thus, [K(+)](o) can be used to assess neural failure. The effect of temperature (17, 23 or 29°C) on the maintenance of brain [K(+)](o) homeostasis in male Drosophila melanogaster (w1118) individuals was assessed during repeated anoxic comas induced by N(2) gas. Brain [K(+)](o) was continuously monitored using K(+)-sensitive microelectrodes while body temperature was changed using a thermoelectric cooler (TEC). Repetitive anoxia resulted in a loss of the ability to maintain [K(+)](o) baseline at 6.6±0.3 mmol l(-1). The total [K(+)](o) baseline variation (Δ[K(+)](o)) was stabilized at 17°C (-1.1±1.3 mmol l(-1)), mildly rose at 23°C (17.3±1.4 mmol l(-1)), and considerably increased at 29°C (332.7±83.0 mmol l(-1)). We conclude that (1) reperfusion patterns consisting of long anoxia, short normoxia and high cycle frequency increase disruption of brain [K(+)](o) baseline maintenance, and (2) hypothermia has a protective effect on brain K(+) homeostasis during repetitive anoxia. Male flies are suggested as a useful model for examining deleterious consequences of O(2) reperfusion with possible application for therapeutic treatment of stroke or heart attack. PMID:22899531

  13. Therapeutic hypothermia for cardiovascular collapse and severe respiratory distress after amniotic fluid embolism.

    PubMed

    Ocegueda-Pacheco, Cynthia; García, J Carlos; Varon, Joseph; Polderman, Kees H

    2014-06-01

    Amniotic fluid embolism (AFE) is one of the most catastrophic complications that can occur during pregnancy or in the immediate postpartum period, frequently complicated by profound shock and cardiovascular collapse as well as severe respiratory distress. Therapeutic hypothermia (TH) is now commonly used to improve neurological outcomes after various types of hypoxic injury and is widely used in the treatment of postanoxic injury after cardiac arrest (CA). To our knowledge, no studies have evaluated whether TH could be effectively used in AFE, and its use for this indication has not been described previously. We describe the case of a 32-year-old woman, who developed clinical manifestations of AFE and suffered a CA in the 29th week of her pregnancy. She received prolonged CPR (40 minutes until ROSC) and remained comatose. TH was induced and maintained for a total of 60 hours using an endovascular device, followed by controlled rewarming and maintenance of strict normothermia. The patient survived and was neurologically intact (CPC 1) at 6 months of follow up. PMID:24670228

  14. Temperature Control During Therapeutic Hypothermia for Newborn Encephalopathy Using Different Blanketrol Devices

    PubMed Central

    Kilbride, Howard; Shepherd, Edward; McDonald, Scott A.; Shankaran, Seetha; Truog, William; Das, Abhik; Higgins, Rosemary D.

    2014-01-01

    Therapeutic hypothermia improves the survival and neurodevelopmental outcome of infants with newborn encephalopathy of a hypoxic-ischemic origin. The NICHD Neonatal Research Network (NRN) Whole Body Cooling trial used the Cincinnati Sub-Zero Blanketrol II to achieve therapeutic hypothermia. The Blanketrol III is now available and provides additional cooling modes that may result in better temperature control. This report is a retrospective comparison of infants undergoing hypothermia using two different cooling modes of the Blanketrol device. Infants from the NRN trial were cooled with the Blanketrol II using the Automatic control mode (B2 cohort) and were compared with infants from two new NRN centers that adopted the NRN protocol and used the Blanketrol III in a gradient mode (B3 cohort). The primary outcome was the percent time the esophageal temperature stayed between 33°C and 34°C (target 33.5°C) during maintenance of hypothermia. Cohorts had similar birth weight, gestational age, and level of encephalopathy at the initiation of therapy. Baseline esophageal temperature differed between groups (36.6°C±1.0°C for B2 vs. 33.9°C±1.2°C for B3, p<0.0001) reflecting the practice of passive cooling during transport prior to initiation of active device cooling in the B3 cohort. This difference prevented comparison of temperatures during induction of hypothermia. During maintenance of hypothermia the mean and standard deviation of the percent time between 33°C and 34°C was similar for B2 compared to B3 cohorts (94.8%±0.1% vs. 95.8%±0.1%, respectively). Both the automatic and gradient control modes of the Blanketrol devices appear comparable in maintaining esophageal temperature within the target range during maintenance of therapeutic hypothermia. PMID:25285767

  15. Hypothermia as a predictor for mortality in trauma patients at admittance to the Intensive Care Unit

    PubMed Central

    Balvers, Kirsten; Van der Horst, Marjolein; Graumans, Maarten; Boer, Christa; Binnekade, Jan M.; Goslings, J. Carel; Juffermans, Nicole P.

    2016-01-01

    Aims: To study the impact of hypothermia upon admission to the Intensive Care Unit (ICU) on early and late mortality and to develop a prediction model for late mortality in severely injured trauma patients. Materials and Methods: A multicenter retrospective cohort study was performed in adult trauma patients admitted to the ICU of two Level-1 trauma centers between 2007 and 2012. Hypothermia was defined as a core body temperature of ≤35° Celsius. Logistic regression analyses were performed to quantify the effect of hypothermia on 24-hour and 28-day mortality and to develop a prediction model. Results: A total of 953 patients were included, of which 354 patients had hypothermia (37%) upon ICU admission. Patients were divided into a normothermic or hypothermic group. Hypothermia was associated with a significantly increased mortality at 24 hours and 28 days (OR 2.72 (1.18-6.29 and OR 2.82 (1.83-4.35) resp.). The variables included in the final prediction model were hypothermia, age, APACHE II score (corrected for temperature), INR, platelet count, traumatic brain injury and Injury Severity Score. The final prediction model discriminated between survivors and non-survivors with high accuracy (AUC = 0.871, 95% CI 0.844-0.898). Conclusions: Hypothermia, defined as a temperature ≤35° Celsius, is common in critically ill trauma patients and is one of the most important physiological predictors for early and late mortality in trauma patients. Trauma patients admitted to the ICU may be at high risk for late mortality if the patient is hypothermic, coagulopathic, severely injured and has traumatic brain injury or an advanced age. PMID:27512330

  16. Treatments (12 and 48 h) with systemic and brain-selective hypothermia techniques after permanent focal cerebral ischemia in rat.

    PubMed

    Clark, Darren L; Penner, Mark; Wowk, Shannon; Orellana-Jordan, Ian; Colbourne, Frederick

    2009-12-01

    Mild hypothermia lessens brain injury when initiated after the onset of global or focal ischemia. The present study sought to determine whether cooling to approximately 33 degrees C provides enduring benefit when initiated 1 h after permanent middle cerebral artery occlusion (pMCAO, via electrocautery) in adult rats and whether protection depends upon treatment duration and cooling technique. In the first experiment, systemic cooling was induced in non-anesthetized rats through a whole-body exposure technique that used fans and water mist. In comparison to normothermic controls, 12- and 48-h bouts of hypothermia significantly lessened functional impairment, such as skilled reaching ability, and lesion volume out to a 1-month survival. In the second experiment, brain-selective cooling was induced in awake rats via a water-cooled metal strip implanted underneath the temporalis muscle overlying the ischemic territory. Use of a 48-h cooling treatment significantly mitigated injury and behavioral impairment whereas a 12-h treatment did not. These findings show that while systemic and focal techniques are effective when initiated after the onset of pMCAO, they differ in efficacy depending upon the treatment duration. A direct and uncomplicated comparison between methods is problematic, however, due to unknown gradients in brain temperature and the use of two separate experiments. In summary, prolonged cooling, even when delayed after onset of pMCAO, provides enduring behavioral and histological protection sufficient to suggest that it will be clinically effective. Nonetheless, further pre-clinical work is needed to improve treatment protocols, such as identifying the optimal depth of cooling, and how these factors interact with cooling method. PMID:19833128

  17. Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain.

    PubMed

    Fukui, On; Kinugasa, Yukiko; Fukuda, Aya; Fukuda, Hirotsugu; Tskitishvili, Ekaterine; Hayashi, Shusaku; Song, Mihyon; Kanagawa, Takeshi; Hosono, Takayoshi; Shimoya, Koichiro; Murata, Yuji

    2006-11-22

    Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in

  18. Hypothermia associated with antipsychotic drug use: a clinical case series and review of current literature.

    PubMed

    Kreuzer, Peter; Landgrebe, Michael; Wittmann, Markus; Schecklmann, Martin; Poeppl, Timm B; Hajak, Goeran; Langguth, Berthold

    2012-07-01

    Hypothermia as an adverse reaction of antipsychotic drug use represents a potentially life-threatening complication. However, the mechanisms by which antipsychotic drugs alter thermoregulatory processes in the human body are far from being fully understood. Here we present a case series of 5 patients developing severe hypothermia after administration of olanzapine and benperidol. Controlled by a network of neural structures, body temperature is physiologically regulated in far more narrow boundaries than are other vital functions, and its homeostasis is critical for survival. The preoptic region in the ventral hypothalamus is assumed to act as a coordinating center that is endowed with thermosensory units that constantly compare actual body temperature with target values and initiate regulatory and compensatory mechanisms in case of mismatch. Hypothermia risk seems to increase in the first days after initiation of antipsychotic drug therapy or increases in the daily dose. Schizophrenic patients bear a higher risk than nonschizophrenic patients treated with antipsychotic drugs (such as patients with dementia or depression). Antipsychotic drugs with strong 5-HT2 antagonism seem to be more frequently associated with hypothermia. These cases demonstrate the clinical relevance of hypothermia as an adverse reaction to antipsychotic treatment and the importance of careful monitoring of body temperature. PMID:21956608

  19. Feasibility and Safety of Therapeutic Hypothermia and Short Term Outcome in Neonates with Hypoxic Ischemic Encephalopathy.

    PubMed

    Purkayastha, Jayashree; Lewis, Leslie Edward; Bhat, Ramesh Y; Anusha, K M

    2016-02-01

    Therapeutic hypothermia is well known for neuroprotection in asphyxiated neonates with hypoxic ischemic encephalopathy. The authors aimed to study the feasibility and safety of therapeutic hypothermia and short term outcome in neonates with hypoxic ischemic encephalopathy (HIE). Total 31 neonates with moderate to severe HIE were enrolled in the study. Continuous temperature recording was noted in 31 neonates; 17 neonates were studied prospectively while 14 neonates were studied retrospectively. Rectal temperature was monitored in 31 neonates and maintained between 33 and 34 °C by switching off the warmer and using ice packs. Reusable ice packs were used which were inexpensive. Therapeutic hypothermia was maintained for 72 h and babies were then rewarmed 0.5 °C every hour. Therapeutic hypothermia was feasible and inexpensive. There was no major complication during the study. MRI was done in 17 neonates; 52 % were found to have normal MRI at the end of first week. Among the study neonates (n = 31) 64.5 % were neurologically normal at the time of discharge. To conclude, therapeutic hypothermia is feasible in a low resource setting and is a safe way of neuroprotection. Short term outcome was also favourable in these neonates. PMID:26141549

  20. Therapeutic Hypothermia in Spinal Cord Injury: The Status of Its Use and Open Questions

    PubMed Central

    Wang, Jiaqiong; Pearse, Damien D.

    2015-01-01

    Spinal cord injury (SCI) is a major health problem and is associated with a diversity of neurological symptoms. Pathophysiologically, dysfunction after SCI results from the culmination of tissue damage produced both by the primary insult and a range of secondary injury mechanisms. The application of hypothermia has been demonstrated to be neuroprotective after SCI in both experimental and human studies. The myriad of protective mechanisms of hypothermia include the slowing down of metabolism, decreasing free radical generation, inhibiting excitotoxicity and apoptosis, ameliorating inflammation, preserving the blood spinal cord barrier, inhibiting astrogliosis, promoting angiogenesis, as well as decreasing axonal damage and encouraging neurogenesis. Hypothermia has also been combined with other interventions, such as antioxidants, anesthetics, alkalinization and cell transplantation for additional benefit. Although a large body of work has reported on the effectiveness of hypothermia as a neuroprotective approach after SCI and its application has been translated to the clinic, a number of questions still remain regarding its use, including the identification of hypothermia’s therapeutic window, optimal duration and the most appropriate rewarming rate. In addition, it is necessary to investigate the neuroprotective effect of combining therapeutic hypothermia with other treatment strategies for putative synergies, particularly those involving neurorepair. PMID:26213924

  1. Hypothermia reduces cerebral metabolic rate and cerebral blood flow in newborn pigs

    SciTech Connect

    Busija, D.W.; Leffler, C.W. )

    1987-10-01

    The authors examined effects of hypothermia on cerebral metabolic rate and cerebral blood flow in anesthetized, newborn pigs (1-4 days old). Cerebral blood flow (CBF) was determined with 15-{mu}m radioactive microspheres. Regional CBF ranged from 44 to 66 ml{center dot}min{sup {minus}1}{center dot}100 g{sup {minus}1}, and cerebral metabolic rate was 1.94 {plus minus} 0.23 ml O{sub 2}{center dot}100 g{sup {minus}1}{center dot}min{sup {minus}1} during normothermia (39{degree}C). Reduction of rectal temperature to 34-35{degree}C decreased CBF and cerebral metabolic rate 40-50%. In another group of piglets, they examined responsiveness of the cerebral circulation to arterial hypercapnia during hypothermia. Although absolute values for normocapnic and hypercapnic CBF were reduced by hypothermia and absolute values for normocapnic and hypercapnic cerebrovascular resistance were increased, the percentage changes from control in these variables during hypercapnia were similar during normothermia and hypothermia. In another group of animals that were maintained normothermic and exposed to two episodes of hypercapnia, there was no attenuation of cerebrovascular dilation during the second episode. They conclude that hypothermia reduces CBF secondarily to a decrease in cerebral metabolic rate and that percent dilator responsiveness to arterial hypercapnia is unaltered when body temperature is reduced.

  2. Hypothermia and afterdrop following open water swimming: the Alcatraz/San Francisco Swim Study.

    PubMed

    Nuckton, T J; Claman, D M; Goldreich, D; Wendt, F C; Nuckton, J G

    2000-10-01

    To determine whether or not participants in open water swim events experience hypothermia and afterdrop, rectal temperature was measured for up to 45 minutes in 11 subjects following the New Year's Day Alcatraz Swim. This event was held in open water (11.7 degrees C [53.0 degrees F]) in the San Francisco Bay, and participants did not wear wetsuits or other protective clothing. Biophysical parameters, including surfacelvolume ratio, body mass index, and percent body fat were measured before the swim, and statistical analysis was done to determine predictors of temperature decrease and afterdrop duration. Applying the American Heart Association definition of hypothermia (less than 36.0 C [96.8 degrees F]), hypothermia was seen in 5 of the 11 subjects. Using a more rigorous and traditional definition (less than 35.0 degrees C [95.0 degrees F]), hypothermia was seen in only one subject. Afterdrop, defined as continued cooling following removal from cold stress, was seen in 10 of the 11 subjects. Surface/volume ratio (S/V) and body mass index (BMI) predicted the lowest recorded temperatures (P < .05; r(S/V) = -.71, r(BMI) = .72) and afterdrop duration (P < .05; r(SN) = -.75, r(BMI) = .69). These results suggest that hypothermia and afterdrop can occur commonly after recreational open water swimming, and that participants should be observed for signs of temperature decrease following removal from cold stress. PMID:11043627

  3. Nocturnal hypothermia impairs flight ability in birds: a cost of being cool.

    PubMed

    Carr, Jennie M; Lima, Steven L

    2013-12-01

    Many birds use regulated drops in night-time body temperature (Tb) to conserve energy critical to winter survival. However, a significant degree of hypothermia may limit a bird's ability to respond to predatory attack. Despite this likely energy-predation trade-off, the behavioural costs of avian hypothermia have yet to be examined. We thus monitored the nocturnal hypothermia of mourning doves (Zenaida macroura) in a laboratory setting in response to food deprivation. Nocturnal flight tests were used to quantify the flight ability of hypothermic doves. Many hypothermic doves (39% of tests) could not fly while carrying a small weight, but could do so after quickly warming up to typical daytime Tb. Doves that were unable to fly during their first test were more hypothermic than those that could fly, with average Tb reductions of 5.3°C and 3.3°C, respectively, but there was no overall indication of a threshold Tb reduction beyond which doves were consistently incapable of flight. These results suggest that energy-saving hypothermia interferes with avian antipredator behaviour via a reduction in flight ability, likely leading to a trade-off between energy-saving hypothermia and the risk of predation. PMID:24107528

  4. Effects of mild hypothermia therapy on the levels of glutathione in rabbit blood and cerebrospinal fluid after cardiopulmonary resuscitation

    PubMed Central

    Zhao, Hui; Chen, Yueliang

    2015-01-01

    Objective(s): The aim of this study was to investigate the effects of mild hypothermia therapy on oxidative stress injury of rabbit brain tissue after cardiopulmonary resuscitation (CPR). Materials and Methods: Rabbit models of cardiac arrest were established. After the restoration of spontaneous circulation, 50 rabbits were randomly divided into normothermia and hypothermia groups. The following five time points were selected: before CPR, immediately after CPR, 2 hr after CPR (hypothermia group reached the target temperature), 14 hr after CPR (hypothermia group before rewarming), and 24 hr after CPR (hypothermia group recovered to normal temperature). Glutathione (GSH) concentrations in both the blood and cerebrospinal fluid of the normothermia and hypothermia groups were measured. Results: At 2, 14, and 24 hr after CPR, the GSH concentrations in both the blood and cerebrospinal fluid were significantly higher in the hypothermia group than in the nomorthermia group. Conclusion: Mild hypothermia therapy may increase GSH concentrations in rabbit blood and cerebrospinal fluid after CPR as well as promote the recovery of cerebral function. PMID:25810895

  5. Sex-specific effects of N-acetylcysteine in neonatal rats treated with hypothermia after severe hypoxia-ischemia.

    PubMed

    Nie, Xingju; Lowe, Danielle W; Rollins, Laura Grace; Bentzley, Jessica; Fraser, Jamie L; Martin, Renee; Singh, Inderjit; Jenkins, Dorothea

    2016-07-01

    Approximately half of moderate to severely hypoxic-ischemic (HI) newborns do not respond to hypothermia, the only proven neuroprotective treatment. N-acetylcysteine (NAC), an antioxidant and glutathione precursor, shows promise for neuroprotection in combination with hypothermia, mitigating post-HI neuroinflammation due to oxidative stress. As mechanisms of HI injury and cell death differ in males and females, sex differences must be considered in translational research of neuroprotection. We assessed the potential toxicity and efficacy of NAC in combination with hypothermia, in male and female neonatal rats after severe HI injury. NAC 50mg/kg/d administered 1h after initiation of hypothermia significantly decreased iNOS expression and caspase 3 activation in the injured hemisphere versus hypothermia alone. However, only females treated with hypothermia +NAC 50mg/kg showed improvement in short-term infarct volumes compared with saline treated animals. Hypothermia alone had no effect in this severe model. When NAC was continued for 6 weeks, significant improvement in long-term neuromotor outcomes over hypothermia treatment alone was observed, controlling for sex. Antioxidants may provide insufficient neuroprotection after HI for neonatal males in the short term, while long-term therapy may benefit both sexes. PMID:26851769

  6. Hypothermia after chronic mild stress exposure in rats with a history of postnatal maternal separations.

    PubMed

    Mrdalj, Jelena; Lundegaard Mattson, Ase; Murison, Robert; Konow Jellestad, Finn; Milde, Anne Marita; Pallesen, Ståle; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

    2014-03-01

    The circadian system develops and changes in a gradual and programmed process over the lifespan. Early in life, maternal care represents an important zeitgeber and thus contributes to the development of circadian rhythmicity. Exposure to early life stress may affect circadian processes and induce a latent circadian disturbance evident after exposure to later life stress. Disturbance of the normal regulation of circadian rhythmicity is surmised to be an etiological factor in depression. We used postnatal maternal separation in rats to investigate how the early life environment might modify the circadian response to later life unpredictable and chronic stress. During postnatal days 2-14, male Wistar rats (n = 8 per group) were daily separated from their mothers for a period of either 180 min (long maternal separation; LMS) or 10 min (brief maternal separation; BMS). In adulthood, rats were exposed to chronic mild stress (CMS) for 4 weeks. Body temperature, locomotor activity and heart rate were measured and compared before and after CMS exposure. LMS offspring showed a delayed body temperature acrophase compared to BMS offspring. Otherwise, adult LMS and BMS offspring demonstrated similar diurnal rhythms of body temperature, locomotor activity and heart rate. Exposure to CMS provoked a stronger and longer lasting hypothermia in LMS rats than in BMS rats. The thermoregulatory response appears to be moderated by maternal care following reunion, an observation made in the LMS group only. The results show that early life stress (LMS) in an early developmental stage induced a thermoregulatory disturbance evident upon exposure to unpredictable adult life stressors. PMID:24156523

  7. Perioperative hypothermia and incidence of surgical wound infection: a bibliographic study

    PubMed Central

    da Silva, Aline Batista; Peniche, Aparecida de Cassia Giani

    2014-01-01

    The purpose of this review article was to understand and analyze the scientific production related to the occurrence of perioperative hypothermia and the incidence of infection on the surgical site. For this purpose, a search was conducted in the databases LILACS, MEDLINE, PubMed, CINAHL and Cochrane, using the health science descriptors DECS, from 2004 to 2009. A total of 91 articles were found. After eliminating duplicate items and using selection criteria for inclusion, six manuscripts remained for analysis. The studies were classified as retrospective, prospective, case studies, and clinical trials. After analysis, the majority of studies showed that hypothermia must be prevented during the perioperative period to reduce complications in the healing process of the surgical incision. Therefore, unadverted hypothermia directly influences in surgical site healing, increasing the incidence of infection in the surgical wound. PMID:25628208

  8. Therapeutic Hypothermia and Out-of-Hospital Cardiac Arrest in a Child with Hypertrophic Obstructive Cardiomyopathy

    PubMed Central

    Spurkeland, Nancy; Bennett, Gregory; Alexander, Chandran; Chang, Dennis; Ceneviva, Gary

    2015-01-01

    Neurologic outcomes following pediatric cardiac arrest are consistently poor. Early initiation of cardiopulmonary resuscitation has been shown to have positive effects on both survival to hospital discharge, and improved neurological outcomes after cardiac arrest. Additionally, the use of therapeutic hypothermia may improve survival in pediatric cardiac arrest patients admitted to the intensive care unit. We report a child with congenital hypertrophic obstructive cardiomyopathy and an out-of-hospital cardiac arrest, in whom the early initiation of effective prolonged cardiopulmonary resuscitation and subsequent administration of therapeutic hypothermia contributed to a positive outcome with no gross neurologic sequelae. Continuing efforts should be made to promote and employ high-quality cardiopulmonary resuscitation, which likely contributed to the positive outcome of this case. Further research will be necessary to develop and solidify national guidelines for the implementation of therapeutic hypothermia in selected subpopulations of children with OHCA. PMID:25861505

  9. [Severe apparent life-threatening event during "skin-to-skin": treatment with hypothermia].

    PubMed

    Marin, N; Valverde, E; Cabañas, F

    2013-10-01

    'Skin-to-skin' in healthy newborn infants is currently routine practice in Spanish maternity wards. This practice has shown benefits in increasing the duration of breast-feeding and maternal bonding behaviour with no significant adverse events. Early sudden deaths and severe apparent life-threatening events (ALTE) during the first 24 hours of life are infrequent, but well recognised. Risk factors during 'skin to skin' have been established. These events can lead to high neonatal morbidity and mortality. Hypothermia is now the standard of care for moderate to severe hypoxic-ischaemic encephalopathy and has shown to reduce mortality and neurological morbidity in children with hypoxic-ischaemic brain injury. Although there are no clinical trials that evaluate hypothermia after a severe ALTE, neonates who suffer it should be considered for this treatment. We present a case of a healthy newborn who had an ALTE during skin-to-skin with his mother and was treated with hypothermia. PMID:24051185

  10. Improving neurological outcome after cardiac arrest: Therapeutic hypothermia the best treatment

    PubMed Central

    Malhotra, Suchitra; Dhama, Satyavir S.; Kumar, Mohinder; Jain, Gaurav

    2013-01-01

    Cardiac arrest, irrespective of its etiology, has a high mortality. This event is often associated with brain anoxia which frequently causes severe neurological damage and persistent vegetative state. Only one out of every six patients survives to discharge following in-hospital cardiac arrest, whereas only 2-9% of patients who experience out of hospital cardiac arrest survive to go home. Functional outcomes of survival are variable, but poor quality survival is common, with only 3-7% able to return to their previous level of functioning. Therapeutic hypothermia is an important tool for the treatment of post-anoxic coma after cardiopulmonary resuscitation. It has been shown to reduce mortality and has improved neurological outcomes after cardiac arrest. Nevertheless, hypothermia is underused in critical care units. This manuscript aims to review the mechanism of hypothermia in cardiac arrest survivors and to propose a simple protocol, feasible to be implemented in any critical care unit. PMID:25885714

  11. Subdural haemorrhage and severe coagulopathy resulting in transtentorial uncal herniation in a neonate undergoing therapeutic hypothermia

    PubMed Central

    Wang, Dianna; McMillan, Hugh; Bariciak, Erika

    2014-01-01

    Therapeutic hypothermia has been shown to be efficacious for improving long-term neurodevelopmental outcomes following perinatal asphyxia. Thus, cooling protocols have been adopted at most tertiary neonatal centres. We present a case of a term neonate who underwent therapeutic whole-body cooling for hypoxic ischaemic encephalopathy following a difficult forceps delivery. She abruptly deteriorated, exhibiting signs of transtentorial uncal herniation and severe disseminated intravascular coagulopathy. CT of the head confirmed a life-threatening subdural haematoma and a concealed skull fracture. Hypothermia has been shown to impair haemostasis in vivo and thus may potentially exacerbate occult haemorrhages in a clinical setting. Newborns that require instrument-assisted delivery are a particularly high-risk group for occult head injuries and should undergo careful clinical assessment for fractures and intracranial haemorrhage prior to initiation of therapeutic hypothermia. PMID:25100805

  12. [The role of therapeutic hypothermia in post-resuscitation care - review of the literature and personal experience].

    PubMed

    Pilecky, Dávid; Szudi, Gábor; Kovács, Enikő; Jenei, Zsigmond; Gellér, László; Heltai, Krisztina; Molnár, Levente; Bárczi, György; Becker, Dávid; Merkely, Béla; Zima, Endre

    2016-04-17

    In the last fifteen years mild therapeutic hypothermia became an accepted and widespread therapeutic method in the treatment of successfully resuscitated patients due to sudden cardiac death. Based on the available evidence therapeutic hypothermia is part of the resuscitation guidelines, however, many aspects of its therapeutic use are based on empirical facts. In particular, the subjects of intense debate are the ideal target temperature and the benefit of hypothermia in patients found with non-shockable rhythm. Hypothermia affects almost all organ systems and, therefore, early detection and treatment of side effects are essential. The aim of the authors is to summarize the clinical role and pathophysiologic effects of therapeutic hypothermia in the treatment of resuscitated patients based on current evidence and their practical experience. PMID:27063428

  13. Does Whole-Body Hypothermia in Neonates with Hypoxic–Ischemic Encephalopathy Affect Surfactant Disaturated-Phosphatidylcholine Kinetics?

    PubMed Central

    Nespeca, Matteo; Giorgetti, Chiara; Nobile, Stefano; Ferrini, Ilaria; Simonato, Manuela; Verlato, Giovanna; Cogo, Paola; Carnielli, Virgilio Paolo

    2016-01-01

    Background It is unknown whether Whole-Body Hypothermia (WBH) affects pulmonary function. In vitro studies, at relatively low temperatures, suggest that hypothermia may induce significant changes to the surfactant composition. The effect of WBH on surfactant kinetics in newborn infants is unknown. We studied in vivo kinetics of disaturated-phosphatidylcholine (DSPC) in asphyxiated newborns during WBH and in normothermic controls (NTC) with no or mild asphyxia. Both groups presented no clinically apparent lung disease. Methods Twenty-seven term or near term newborns requiring mechanical ventilation were studied (GA 38.6±2.2 wks). Fifteen during WBH and twelve NTC. All infants received an intra-tracheal dose of 13C labelled DSPC and tracheal aspirate were performed. DSPC amount, DSPC half-life (HL) and pool size (PS) were calculated. Results DSPC amount in tracheal aspirates was 0.42 [0.22–0.54] and 0.36 [0.10–0.58] mg/ml in WBH and NTC respectively (p = 0.578). DSPC HL was 24.9 [15.7–52.5] and 25.3 [15.8–59.3] h (p = 0.733) and DSPC PS was 53.2 [29.4–91.6] and 40.2 [29.8–64.6] mg/kg (p = 0.598) in WBH and NTC respectively. Conclusions WBH does not alter DSPC HL and PS in newborn infants with no clinical apparent lung disease. PMID:27070307

  14. Better Glasgow outcome score, cerebral perfusion pressure and focal brain oxygenation in severely traumatized brain following direct regional brain hypothermia therapy: A prospective randomized study

    PubMed Central

    Idris, Zamzuri; Zenian, Mohd Sofan; Muzaimi, Mustapha; Hamid, Wan Zuraida Wan Abdul

    2014-01-01

    Background: Induced hypothermia for treatment of traumatic brain injury is controversial. Since many pathways involved in the pathophysiology of secondary brain injury are temperature dependent, regional brain hypothermia is thought capable to mitigate those processes. The objectives of this study are to assess the therapeutic effects and complications of regional brain cooling in severe head injury with Glasgow coma scale (GCS) 6-7. Materials and Methods: A prospective randomized controlled pilot study involving patients with severe traumatic brain injury with GCS 6 and 7 who required decompressive craniectomy. Patients were randomized into two groups: Cooling and no cooling. For the cooling group, analysis was made by dividing the group into mild and deep cooling. Brain was cooled by irrigating the brain continuously with cold Hartmann solution for 24-48 h. Main outcome assessments were a dichotomized Glasgow outcome score (GOS) at 6 months posttrauma. Results: A total of 32 patients were recruited. The cooling-treated patients did better than no cooling. There were 63.2% of patients in cooling group attained good GOS at 6 months compared to only 15.4% in noncooling group (P = 0.007). Interestingly, the analysis at 6 months post-trauma disclosed mild-cooling-treated patients did better than no cooling (70% vs. 15.4% attained good GOS, P = 0.013) and apparently, the deep-cooling-treated patients failed to be better than either no cooling (P = 0.074) or mild cooling group (P = 0.650). Conclusion: Data from this pilot study imply direct regional brain hypothermia appears safe, feasible and maybe beneficial in treating severely head-injured patients. PMID:25685201

  15. Liquid ventilator for ultrafast hypothermia induction in juvenile lambs: Preliminary results.

    PubMed

    Nadeau, Mathieu; Sage, Michaël; Kohlhauer, Matthias; Robert, Raymond; Vandamne, Jonathan; Mousseau, Julien; Tissier, Renaud; Praud, Jean-Paul; Walti, Hervé; Micheau, Philippe

    2015-08-01

    Total liquid ventilation (TLV) is an emerging mechanical ventilation technique. In this technique, the lungs are filled with liquid perfluorocarbons (PFC) and a liquid ventilator assures ventilation by periodically renewing a volume of oxygenated, CO2 freed and temperature controlled PFC. A huge difference between conventional mechanical ventilation and TLV relates to the fact that PFCs are about 1500 times denser than air. Thus, the PFCs filled lungs turn into an efficient heat exchanger with the circulating blood. One of the most appealing utilization of the lungs as a heat exchanger in TLV is for ultrafast induction of mild therapeutic hypothermia (MTH) for neuroprotection and cardioprotection after ischemia-reperfusion injuries. This study aimed to perform ultrafast MTH induction by TLV in animals up to 25 kg, then perform a fast post-hypothermic rewarming while maintaining proper ventilation. A thermal model of the lamb and liquid ventilator was developed to predict the dynamic and the control strategy to adopt for MTH induction. Two juvenile lambs were instrumented with temperature sensors in the femoral artery, pulmonary artery, oesophagus, right eardrum and rectum. After stabilization in conventional mechanical ventilation, TLV was initiated with ultrafast MTH induction, followed by posthypothermic rewarming. Preliminary results in the two juvenile lambs reveal that the liquid ventilator Inolivent-6.0 can induce MTH by TLV in less than 2.5 min for systemic arterial blood and in less than 10 min for venous return, esophagus and eardrum. Rectal temperature reached MTH in respectively 19.4 and 17.0 min for both lambs. Experimental results were consistent with the model predictions. Moreover, blood gas analysis exhibited that the gas exchange in the lungs was maintained adequately for the entire experiments. PMID:26736603

  16. Opposite effects of GABAA and NMDA receptor antagonists on ethanol-induced behavioral sleep in rats.

    PubMed

    Beleslin, D B; Djokanović, N; Jovanović Mićić, D; Samardzić, R

    1997-01-01

    The effects of the GABAA receptor antagonists, pentylenetetrazol, bicuculline, and picrotoxin, the glycine antagonist, strychnine, and the NMDA receptor antagonist, memantine, on ethanol-induced behavioral sleep and body temperature were investigated. Pentylenetetrazol, bicuculline, and picrotoxin given prior and following ethanol reduced the behavioral sleep and potentiated the hypothermia caused by ethanol. However, convulsions appeared when bicuculline, but not pentylenetetrazol and picrotoxin, were given following ethanol. After the reversal of unconsciousness in rats without convulsions the animals remained awake throughout the experiments without motor incoordination, hyperexcitability, and sedation, but they were in hypothermia within 12 h. The glycine antagonist, strychnine, given prior or after ethanol had virtually no effect on ethanol-induced behavioral sleep and hypothermia. Ethanol given prior or following strychnine failed to antagonize strychnine-induced convulsions. The NMDA receptor antagonist, memantine, given following ethanol potentiated the behavioral sleep and had virtually no effect on hypothermia induced by ethanol. It is suggested that the ethanol-induced behavioral sleep may be attributed to its ability to enhance the GABAergic mechanisms and to inhibit NMDA-mediated excitatory responses. However, the ethanol-induced hypothermia may be ascribed solely to the facilitation of GABAergic transmission. Further, it is postulated that a bidirectional inhibitory system subserves the regulation of behavioral sleep and convulsions. However, one-way inhibitory system underlies the ethanol-induced hypothermia. PMID:9085718

  17. Therapeutic hypothermia after in-hospital cardiac arrest: a critique.

    PubMed

    Hessel, Eugene A

    2014-06-01

    More than 210,000 in-hospital cardiac arrests occur annually in the United States. Use of moderate therapeutic hypothermia (TH) in comatose survivors after return of spontaneous circulation following out-of-hospital cardiac arrest (OOH-CA) caused by ventricular fibrillation or pulseless ventricular tachycardia is recommended strongly by many professional organizations and societies. The use of TH after cardiac arrest associated with nonshockable rhythms and after in-hospital cardiac arrest (IH-CA) is recommended to be considered by these same organizations and is being applied widely. The use in these latter circumstances is based on an extrapolation of the data supporting its use after out-of-hospital cardiac arrest associated with shockable rhythms. The purpose of this article is to review the limitations of existing data supporting these extended application of TH after cardiac arrest and to suggest approaches to this dilemma. The data supporting its use for OOH-CA appear to this author, and to some others, to be rather weak, and the data supporting the use of TH for IH-CA appear to be even weaker and to include no randomized controlled trials (RCTs) or supportive observational studies. The many reasons why TH might be expected to be less effective following IH-CA are reviewed. The degree of neurologic injury may be more severe in many of these cases and, thus, may not be responsive to TH as currently practiced following OOH-CA. The potential adverse consequences of the routine use of TH for IH-CA are listed and include complications associated with TH, interference with diagnostic and interventional therapy, and use of scarce personnel and financial resources. Most importantly, it inhibits the ability of researchers to conduct needed RCTs. The author believes that the proper method of providing TH in these cases needs to be better defined. Based on this analysis the author concludes that TH should not be used indiscriminantly following most cases of IH-CA, and

  18. Asystolic Cardiac Arrest of Unknown Duration in Profound Hypothermia and Polysubstance Overdose: A Case Report of Complete Recovery

    PubMed Central

    Lubana, Sandeep Singh; Genin, Dennis Iilya; Singh, Navdeep; De La Cruz, Angel

    2015-01-01

    Patient: Male, 20 Final Diagnosis: Asystolic cardiac arrest in profound hypothermia and poly-substance overdose Symptoms: Cardiac arrest • cardiac arrhythmia Medication: — Clinical Procedure: Endotracheal intubation • hemodialysis Specialty: Critical Care Medicine Objective: Unusual clinical course Background: Opioid addiction and overdose is a serious problem worldwide. Fatal overdoses from opioids are responsible for numerous deaths and are increasing, especially if taken in combination with other psychoactive substances. Combined with environmental exposure, opioid overdose can cause profound hypothermia. Opioid abuse and other drugs of abuse impair thermoregulation, leading to severe hypothermia. Both drug overdose and severe hypothermia can cause cardiac arrest. Case Report: We report a case of 20-year-old man with history of polysubstance abuse presenting with severe hypothermia and asystole of unknown duration with return of spontaneous circulation (ROSC) achieved after 28 minutes of cardiopulmonary resuscitation (CPR). Urine toxicology was positive for cocaine, heroin, and benzodiazepine, along with positive blood alcohol level. The patient was rewarmed using non-invasive techniques. Hospital course was complicated by acute renal failure (ARF), severe rhabdomyolysis, severe hyperkalemia, ST-elevation myocardial infarction (STEMI), shock liver, coagulopathy, and aspiration pneumonia. Conclusions: Survival with full cardiovascular and neurologic recovery after a cardiac arrest caused by drug overdose in the setting of severe hypothermia is still possible, even if the cardiac arrest is of unknown or prolonged duration. Patients with severe hypothermia experiencing cardiac arrest/hemodynamic instability can be rewarmed using non-invasive methods and may not necessarily need invasive rewarming techniques. PMID:26054008

  19. Extending the duration of hypothermia does not further improve white matter protection after ischemia in term-equivalent fetal sheep

    PubMed Central

    Davidson, Joanne O.; Yuill, Caroline A.; Zhang, Frank G.; Wassink, Guido; Bennet, Laura; Gunn, Alistair J.

    2016-01-01

    A major challenge in modern neonatal care is to further improve outcomes after therapeutic hypothermia for hypoxic ischemic encephalopathy. In this study we tested whether extending the duration of cooling might reduce white matter damage. Term-equivalent fetal sheep (0.85 gestation) received either sham ischemia followed by normothermia (n = 8) or 30 minutes of bilateral carotid artery occlusion followed by three days of normothermia (n = 8), three days of hypothermia (n = 8) or five days of hypothermia (n = 8) started three hours after ischemia. Histology was assessed 7 days after ischemia. Ischemia was associated with loss of myelin basic protein (MBP) and Olig-2 positive oligodendrocytes and increased Iba-1-positive microglia compared to sham controls (p < 0.05). Three days and five days of hypothermia were associated with a similar, partial improvement in MBP and numbers of oligodendrocytes compared to ischemia-normothermia (p < 0.05). Both hypothermia groups had reduced microglial activation compared to ischemia-normothermia (p < 0.05). In the ischemia-five-day hypothermia group, but not ischemia-three-day, numbers of microglia remained higher than in sham controls (p < 0.05). In conclusion, delayed cerebral hypothermia partially protected white matter after global cerebral ischemia in fetal sheep. Extending cooling from 3 to 5 days did not further improve outcomes, and may be associated with greater numbers of residual microglia. PMID:27121655

  20. When, where and how to initiate hypothermia after adult cardiac arrest.

    PubMed

    Taccone, F S; Donadello, K; Beumier, M; Scolletta, S

    2011-09-01

    Therapeutich hypothermia (TH) has been shown to improve neurological outcome and survival after witnessed cardiac arrest (CA) that is due to ventricular fibrillation. Although TH is widely used following witnessed CA as well as all forms of initial rhythm, the mortality rate after CA remains unacceptably high, and additional study is needed to understand when and how to implement hypothermia in the post-resuscitation phase. Experimental studies have emphasized the importance of initiating cooling soon after the return of spontaneous circulation (ROSC) or even during cardiopulmonary resuscitation (CPR). Clinical studies have shown that pre-hospital induction of hypothermia is feasible and has no major adverse events-even when used intra-arrest-and may provide some additional benefits compared to delayed in-hospital cooling. Thus, hypothermia use should not be limited to the Intensive Care Unit but can be initiated in the field/ambulance or in the Emergency Department, then continued after hospital admission- even during specific procedures such as coronary angiography-as part of the global management of CA patients. Various methods (both non-invasive and invasive) are available to achieve and maintain the target temperature; however, only some of these methods-which include cold fluids, ice packs, iced pads and helmet and trans-nasal cooling- are easily deployed in the pre-hospital setting. PMID:21878875

  1. Prevention of perioperative hypothermia with forced-air warming systems and upper-body blankets.

    PubMed

    Perl, Thorsten; Bräuer, Anselm; Quintel, Michael

    2006-01-01

    Forced-air warming is known as an effective procedure in prevention and treatment of perioperative hypothermia. Hypothermia is associated with disturbances of coagulation, raises postoperative oxygen consumption by shivering, increases cardiac morbidity, leads to a higher incidence of wound infection, and prolongs hospital stay. Additionally, preoperative local warming reduces the incidence of wound infection after clean surgery. In an animal experiment it has been demonstrated that even during large abdominal operations the major source of heat loss was the skin. Although evaporation accounted for the largest heat loss from the abdominal cavity, it was a minor source due to the smaller heat losing area. As a consequence, reduction of heat loss from the skin is the most promising approach to avoid hypothermia. During abdominal surgery and lower-limb surgery, the use of upper blankets is favourable. The use of upper-body blankets implies a reduction of heat loss in a relevant area and, furthermore, a heat gain. The covered area is approximately 0.35 m2, or approximately 15%-20% of body surface. The heat balance in this area can be changed by 46.1W to 55.0W by forced-air warming systems with upper body blankets. Depending on the surgical procedure and resulting fluid demand, forced-air warming with upper-body blankets-in combination with insulation and fluid warming-is an effective method to prevent perioperative hypothermia. PMID:17029156

  2. DIFFERENTIAL IMPACT OF HYPOTHERMIA AND PENTOBARBITAL ON BRAINSTEM AUDITORY EVOKED RESPONSE

    EPA Science Inventory

    Two experiments were conducted to determine the effects of hypothermia and pentobarbital anesthesia, alone and in combination, on the brainstem auditory evoked responses (BAERs) of rats. n experiment I, unanesthetized rats were cooled to colonic temperatures 0.5 and 1.0 degrees C...

  3. Changes in Surface Charge Density of Blood Cells in Fatal Accidental Hypothermia.

    PubMed

    Szeremeta, Michał; Petelska, Aneta Dorota; Kotyńska, Joanna; Pepiński, Witold; Naumowicz, Monika; Figaszewski, Zbigniew Artur; Niemcunowicz-Janica, Anna

    2015-12-01

    The objective of this research was to evaluate postmortem changes concerning electric charge of human erythrocytes and thrombocytes in fatal accidental hypothermia. The surface charge density values were determined on the basis of the electrophoretic mobility measurements of the cells conducted at various pH values of electrolyte solution. The surface charge of erythrocyte membranes after fatal accidental hypothermia increased compared to the control group within whole range of experimental pH values. Moreover, a slight shift of the isoelectric point of erythrocyte membranes towards high pH values was observed. The surface charge of thrombocyte membranes in fatal accidental hypothermia decreased at low pH compared to the control group. However, at pH range 4-9, the values increased compared to the control group. The isoelectric point of thrombocyte membranes after fatal accidental hypothermia was slightly shifted towards low pH values compared to the control group. The observed changes are probably connected with the partial destruction and functional changes of the blood cell structure. PMID:26364031

  4. Therapeutic Hypothermia for Neonatal Hypoxic–Ischemic Encephalopathy – Where to from Here?

    PubMed Central

    Davidson, Joanne O.; Wassink, Guido; van den Heuij, Lotte G.; Bennet, Laura; Gunn, Alistair J.

    2015-01-01

    Hypoxia–ischemia before or around the time of birth occurs in approximately 2/1000 live births and is associated with a high risk of death or lifelong disability. Therapeutic hypothermia is now well established as standard treatment for infants with moderate to severe hypoxic–ischemic encephalopathy but is only partially effective. There is compelling preclinical and clinical evidence that hypothermia is most protective when it is started as early as possible after hypoxia–ischemia. Further improvements in outcome from therapeutic hypothermia are very likely to arise from strategies to reduce the delay before starting treatment of affected infants. In this review, we examine evidence that current protocols are reasonably close to the optimal depth and duration of cooling, but that the optimal rate of rewarming after hypothermia is unclear. The potential for combination treatments to augment hypothermic neuroprotection has considerable promise, particularly with endogenous targets such as melatonin and erythropoietin, and noble gases such as xenon. We dissect the critical importance of preclinical studies using realistic delays in treatment and clinically relevant cooling protocols when examining combination treatment, and that for many strategies overlapping mechanisms of action can substantially attenuate any effects. PMID:26441818

  5. Drugs and alcohol in hypothermia and hyperthermia related deaths: a retrospective study.

    PubMed

    Kortelainen, M L

    1987-11-01

    Hypothermia and hyperthermia related cases recorded for the period 1973 to 1984 were collected from the files of the Department of Forensic Medicine, University of Oulu, and the necropsy protocols including toxicological results were analyzed. The fact that similar alcohol concentrations were found in both types of fatalities points to the poikilothermic effect of alcohol in humans, as found in animal studies. Both types of deaths seem to be associated with the alcohol elimination phase. Antidepressants and neuroleptics were most often found in the hypothermia cases, but benzodiazepines were also quite frequently present. In spite of the diminished use of barbiturates, these still appear in hypothermia fatalities. Certain other drugs that affect thermoregulation were also noted in solitary cases. Extended toxicological analysis was seldom made in the cases of hyperthermia deaths, and no firm conclusions on the poikilothermic effect of psychotropic drugs could be reached, for example. Therapeutic drug concentrations did not alone predispose the subjects to hypothermia, but appeared in connection with alcohol consumption or chronic diseases. PMID:3430138

  6. Thermal management during anaesthesia and thermoregulation standards for the prevention of inadvertent perioperative hypothermia.

    PubMed

    Torossian, Alexander

    2008-12-01

    Incidence of inadvertent perioperative hypothermia is still high, and thus thermoregulatory standards are warranted. This review summarizes current evidence of thermal management during anaesthesia, referring to recognized clinical queries (temperature measurement, definition of hypothermia, risk factors, warming methods, implementation strategies). Body temperature is a vital sign, and 37 degrees C is the mean core temperature of a healthy human. Systematic review shows that for non-invasive temperature monitoring the oral route is the most reliable; infrared ear temperature measurement is inaccurate. Intraoperatively, acceptable semi-invasive temperature monitoring sites are the nasopharynx, oesophagus and urinary bladder. Clinically relevant hypothermia starts at 36 degrees C with regard to major adverse outcomes (increased infectious complications, morbid cardiac events, coagulation disorders, prolonged length of hospital stay, and increased costs). Skin surface warming for 20 min immediately before anaesthesia (pre-warming) minimizes initial redistribution hypothermia. Intraoperatively, active warming should be applied when anaesthesia time is > 60 min. Effective methods of active warming are forced-air warming or conductive warming, provided that enough skin surface is available. Infusion fluid warming, increasing the operating room temperature, and warming of irrigation fluids are adjunctive therapies. The patient's body temperature should be above 36 degrees C before induction of anaesthesia, and should be measured continuously throughout surgery. Active warming should be applied intraoperatively. Postoperative patient temperature and outcomes should be evaluated. PMID:19137809

  7. Shallow hypothermia depends on the level of fatty acid unsaturation in adipose and liver tissues in a tropical heterothermic primate.

    PubMed

    Vuarin, Pauline; Henry, Pierre-Yves; Guesnet, Philippe; Alessandri, Jean-Marc; Aujard, Fabienne; Perret, Martine; Pifferi, Fabien

    2014-07-01

    Optimal levels of unsaturated fatty acids have positive impacts on the use of prolonged bouts of hypothermia in mammalian hibernators, which generally have to face low winter ambient temperatures. Unsaturated fatty acids can maintain the fluidity of fat and membrane phospholipids at low body temperatures. However, less attention has been paid to their role in the regulation of shallow hypothermia, and in tropical species, which may be challenged more by seasonal energetic and/or water shortages than by low temperatures. The present study assessed the relationship between the fatty acids content of white adipose and liver tissues and the expression of shallow hypothermia in a tropical heterothermic primate, the gray mouse lemur (Microcebus murinus). The adipose tissue is the main tissue for fat storage and the liver is involved in lipid metabolism, so both tissues were expected to influence hypothermia dependence on fatty acids. As mouse lemurs largely avoid deep hypothermia (i.e. torpor) use under standard captive conditions, the expression of hypothermia was triggered by food-restricting experimental animals. Hypothermia depth increased with time, with a stronger increase for individuals that exhibited higher contents of unsaturated fatty acids suggesting that they were more flexible in their use of hypothermia. However these same animals delayed the use of long hypothermia bouts relative to individuals with a higher level of saturated fatty acids. This study evidences for the first time that body fatty acids unsaturation levels influence the regulation of body temperature not only in cold-exposed hibernators but also in tropical, facultative heterotherms. PMID:24956961

  8. BIOMARKERS S100B AND NSE PREDICT OUTCOME IN HYPOTHERMIA-TREATED ENCEPHALOPATHIC NEWBORNS

    PubMed Central

    Massaro, An N.; Chang, Taeun; Baumgart, Stephen; McCarter, Robert; Nelson, Karin B.; Glass, Penny

    2014-01-01

    Objective To evaluate if serum S100B protein and neuron specific enolase (NSE) measured during therapeutic hypothermia are predictive of neurodevelopmental outcome at 15 months in children with neonatal encephalopathy (NE). Design Prospective longitudinal cohort study Setting A level IV neonatal intensive care unit in a free-standing children’s hospital. Patients Term newborns with moderate to severe NE referred for therapeutic hypothermia during the study period. Interventions Serum NSE and S100B were measured at 0, 12, 24 and 72 hrs of hypothermia. Measurements and Main Reseults Of the 83 infants were enrolled, fifteen (18%) died in the newborn period. Survivors were evaluated by the Bayley Scales of Infant Development (BSID-II) at 15 months of age. Outcomes were assessed in 49/68 (72%) survivors at a mean age of 15.2±2.7 months. Neurodevelopmental outcome was classified by BSID-II Mental (MDI) and Psychomotor (PDI) Developmental Index scores, reflecting cognitive and motor outcomes respectively. Four-level outcome classifications were defined a priori: normal= MDI/PDI within 1SD (>85), mild= MDI/PDI <1SD (70–85), moderate/severe= MDI/PDI <2SD (<70), or died. Elevated serum S100B and NSE levels measured during hypothermia were associated with increasing outcome severity after controlling for baseline and soceioeconomic characteristics in ordinal regression models. Adjusted odds ratios for cognitive outcome were: S100B 2.5 (95% CI 1.3–4.8) and NSE 2.1 (1.2–3.6); for motor outcome: S100B 2.6 (1.2–5.6) and NSE 2.1 (1.2–3.6). Conclusions Serum S100B and NSE levels in babies with NE are associated with neurodevelopmental outcome at 15 months. These putative biomarkers of brain injury may help direct care during therapeutic hypothermia. PMID:24777302

  9. Localized hypothermia: impact on oxygenation, microregional perfusion, metabolic and bioenergetic status of subcutaneous rat tumours.

    PubMed Central

    Kelleher, D. K.; Nauth, C.; Thews, O.; Krueger, W.; Vaupel, P.

    1998-01-01

    The effect of localized hypothermia on microcirculatory and metabolic parameters in s.c. DS sarcomas on the hind foot dorsum of Sprague-Dawley rats was investigated. Tumours were cooled by superfusion of the tumour surface with cooled saline solution to 25 degrees C or 15 degrees C. Control tumours remained at 35 degrees C. These temperatures were maintained for 30 min. In tumour oxygenation measurements, hypothermia at 25 degrees C and 15 degrees C caused progressive decreases in the size of the fraction of pO2 measurements between 0 and 2.5 mmHg together with a reduction in pO2 variability. No significant changes in median or mean pO2 or in the fraction of pO2 measurements between 0 and 5 mmHg, and 0 and 10 mmHg were observed. Using laser Doppler flowmetry, red blood cell flux was found to decrease significantly upon 25 degrees C or 15 degrees C hypothermia treatment to 67% and 37% of starting values respectively, whereas no significant changes were seen in control tumours over the whole observation period. Viscosity was measured in blood and plasma samples over a range of temperatures and was found to increase with decreasing temperature. Assessment of tumour glucose levels showed an increased concentration of glucose following 15 degrees C hypothermia, an observation consistent with a 'slowing down' of glycolysis. No changes in lactate or adenylate phosphate levels were observed. As a way of improving tumour oxygenation, localized hypothermia may therefore be a useful means of radiosensitization. PMID:9662251

  10. HYPOTHERMIA AND HYPOMETABOLISM: SENSITIVE INDICES OF WHOLE-BODY TOXICITY FOLLOWING EXPOSURE TO METALLIC SALTS IN THE MOUSE

    EPA Science Inventory

    To investigate the practicality of hypothermia and hypometabolism as sensitive indices of toxicity in the mouse, oxygen consumption was monitored continuously and body temperature was measured at 30 min post-injection following the intraperitoneal administration of various metal ...

  11. Number needed to treat = six: therapeutic hypothermia following cardiac arrest – an effective and cheap approach to save lives

    PubMed Central

    Böttiger, Bernd W; Schneider, Andreas; Popp, Erik

    2007-01-01

    In 2005, the European Resuscitation Council (ERC) guidelines stated: Unconscious adult patients with spontaneous circulation after out-of-hospital ventricular fibrillation cardiac arrest should be cooled to 32 to 34°C for 12 to 24 hours. Patients with cardiac arrest from a non-shockable rhythm, in-hospital patients and children may also benefit from hypothermia. There is no argument to wait. We have to treat the next unconscious cardiac arrest patient with hypothermia. PMID:17850681

  12. Mild Hypothermia Combined with Hydrogen Sulfide Treatment During Resuscitation Reduces Hippocampal Neuron Apoptosis Via NR2A, NR2B, and PI3K-Akt Signaling in a Rat Model of Cerebral Ischemia-Reperfusion Injury.

    PubMed

    Dai, Hai-Bin; Xu, Miao-Miao; Lv, Jia; Ji, Xiang-Jun; Zhu, Si-Hai; Ma, Ru-Meng; Miao, Xiao-Lei; Duan, Man-Lin

    2016-09-01

    We investigated whether mild hypothermia combined with sodium hydrosulfide treatment during resuscitation improves neuron survival following cerebral ischemia-reperfusion injury beyond that observed for the individual treatments. Male Sprague-Dawley rats were divided into seven groups (n = 20 for each group). All rats underwent Pulsinelli 4-vessel occlusion. Ischemia was induced for 15 min using ligatures around the common carotid arteries, except for the sham group. Immediately after initiating reperfusion, the mild hypothermia (MH), sodium hydrosulfide (NaHS), hydroxylamine (HA), MH + NaHS, MH + HA, and ischemia-reperfusion (I/R) control groups received an intraperitoneal injection of saline, sodium hydrosulfide, hydroxylamine, sodium hydrosulfide, hydroxylamine, and saline, respectively, and mild hypothermia (32 to 33 °C) was induced in the MH, MH + NaHS, and MH + HA groups for 6 h. The levels of NR2A, NR2B, p-Akt, and p-Gsk-3β in the hippocampus of the MH, NaHS, and MH + NaHS groups were higher than those in the I/R control group, with the highest levels observed in the MH + NaHS group (P < 0.05). Treatment with hydroxylamine reduced the levels of these proteins in the HA and MH + HA groups, compared with the I/R control and MH groups, respectively. The apoptotic index of the CA1 region of the hippocampus was 45.2, 66.5, 63.5, and 84.8 % in the MH + NaHS, MH, NaHS, and I/R control groups, respectively (P < 0.05), indicating that the combination treatment shifted the NR2A/NR2B balance in favor of synaptic neuron stimulation and phosphatidylinositol 3'-kinase (PI3K)/Akt signaling. The combination of mild hypothermia and sodium hydrosulfide treatment for resuscitation following ischemia-reperfusion injury was more beneficial for reducing hippocampal apoptosis and pathology than that of mild hypothermia or hydrogen sulfide treatment alone. PMID:26350917

  13. Therapeutic Hypothermia as a Neuroprotective Strategy in Neonatal Hypoxic-Ischemic Brain Injury and Traumatic Brain Injury

    PubMed Central

    Ma, H.; Sinha, B.; Pandya, R.S.; Lin, N.; Popp, A.J.; Li, J.; Yao, J.; Wang, X.

    2014-01-01

    Evidence shows that artificially lowering body and brain temperature can significantly reduce the deleterious effects of brain injury in both newborns and adults. Although the benefits of therapeutic hypothermia have long been known and applied clinically, the underlying molecular mechanisms have yet to be elucidated. Hypoxic-ischemic brain injury and traumatic brain injury both trigger a series of biochemical and molecular events that cause additional brain insult. Induction of therapeutic hypothermia seems to ameliorate the molecular cascade that culminates in neuronal damage. Hypothermia attenuates the toxicity produced by the initial injury that would normally produce reactive oxygen species, neurotransmitters, inflammatory mediators, and apoptosis. Experiments have been performed on various depths and levels of hypothermia to explore neuroprotection. This review summarizes what is currently known about the beneficial effects of therapeutic hypothermia in experimental models of neonatal hypoxic-ischemic brain injury and traumatic brain injury, and explores the molecular mechanisms that could become the targets of novel therapies. In addition, this review summarizes the clinical implications of therapeutic hypothermia in newborn hypoxic-ischemic encephalopathy and adult traumatic brain injury. PMID:22834830

  14. An experimental model for the study of transcapillary fluid balance in hypothermia.

    PubMed

    Skandfer, M; Tveita, T; Oian, P; Ytrehus, K; Refsum, H

    1991-01-01

    Disturbed fluid balance is a significant clinical problem in hypothermia and rewarming. We have therefore investigated whether the transcapillary fluid balance in rats exposed to hypothermia and rewarming could be studied with the use of a wick method. Double nylon wicks were sewn into the abdominal skin and left there for one hour, then removed to double-bottomed conic vials and centrifuged. Wick fluid was collected and colloid osmotic pressure measured. Blood samples were taken simultaneously for measurement of hematocrit, hemoglobin, red cell count and plasma colloid osmotic pressure. This was done at 37 degrees C (prehypothermic), 13 degrees C (hypothermic) and at 30 degrees C (during rewarming). Blood pressure was also recorded. The model provides a good method to investigate the colloid osmotic changes of both plasma and interstitium during hypothermic situations. PMID:1811566

  15. Concurrent erythropoietin and hypothermia treatment improve outcomes in a term nonhuman primate model of perinatal asphyxia

    PubMed Central

    Traudt, Christopher M.; McPherson, Ronald J.; Bauer, Larry A.; Richards, Todd L.; Burbacher, Thomas M.; McAdams, Ryan M.; Juul, Sandra E.

    2013-01-01

    Background Up to 65% of untreated infants suffering from moderate to severe hypoxic-ischemic encephalopathy (HIE) are at risk of death or major disability. Therapeutic hypothermia (HT) reduces this risk to approximately 50% (number needed to treat 7-9). Erythropoietin (Epo) is a neuroprotective treatment that is promising as an adjunctive therapy to decrease HIE-induced injury because Epo decreases apoptosis, inflammation, and oxidative injury, and promotes glial cell survival, and angiogenesis. We hypothesized that HT and concurrent Epo will be safe, effective, improve survival and reduce moderate-severe cerebral palsy (CP) in a term nonhuman primate model of perinatal asphyxia. Methodology 35 Macaca nemestrina were delivered after 15-18 min of umbilical cord occlusion (UCO) and randomized to saline (n=14), HT only (n=9) or HT+Epo (n=12). There were 12 unasphyxiated controls. Epo (3500 U/kg × 1 followed by 3 doses of 2500 U/Kg, or Epo 1000 U/kg/d × 4 doses) was given on days 1, 2, 3, and 7. Timed blood samples were collected to measure plasma Epo concentrations. Animals underwent MRI/MRS and diffusion tensor imaging (DTI) at < 72 hours of age and again at 9 months. A battery of weekly developmental assessments was performed. Results UCO resulted in death or moderate-severe CP in 43% of saline, 44% of HT, and 0% of HT+Epo treated animals. Compared to non-UCO control animals, UCO animals exhibit poor weight gain, behavioral impairment, poor cerebellar growth and abnormal brain DTI. Compared to UCO saline, UCO HT+Epo improved motor and cognitive responses, cerebellar growth, DTI measures, and produced a death/disability relative risk reduction of 0.911 (95% CI −0.429 to 0.994), an absolute risk reduction of 0.395 (95% CI 0.072 to 0.635), and a number needed to treat of 2 (95% CI 14 to 2). HT+Epo effects on DTI included improved mode of anisotropy, fractional anisotropy, relative anisotropy and volume ratio as compared to UCO saline treated infants. No adverse

  16. The pathophysiological mechanisms of the onset of death through accidental hypothermia and the presentation of “The little match girl” case

    PubMed Central

    JEICAN, IONUŢ ISAIA

    2014-01-01

    Hypothermia and death caused by hypothermia may be found in a number of fiction works, mainly in novels. In the well-known story “The Little Match Girl” by Hans Christian Andersen, one can notice that the descriptions of the phenomena occurring before the girl’s death are in fact a literary presentation of the pathophysiological mechanisms of the onset of death through accidental hypothermia. This essay presents the medical aspects of the story written by Andersen. PMID:26527999

  17. In vivo Monitoring of Cerebral Hemodynamics in the Immature Rat: Effects of Hypoxia-Ischemia and Hypothermia

    PubMed Central

    Buckley, Erin M.; Patel, Shyama D.; Miller, Benjamin F.; Franceschini, Maria Angela; Vannucci, Susan J.

    2015-01-01

    Background Neonatal hypoxic-ischemic (HI) encephalopathy occurs in 1–4 per 1,000 live term births and can cause devastating neurodevelopmental disabilities. Currently, therapeutic hypothermia (TH) is the only treatment with proven efficacy. Since TH is associated with decreased cerebral metabolism and cerebral blood flow (CBF), it is important to assess CBF at the bedside. Diffuse correlation spectroscopy (DCS) has emerged as a promising optical modality to noninvasively assess an index of CBF (CBFi) in both humans and animals. In this initial descriptive study, we employ DCS to monitor the evolution of CBFi following HI with or without TH in immature rats. We investigate potential relationships between CBF and subsequent cerebral damage. Methods HI was induced on postnatal day 10 or 11 rat pups by right common carotid artery ligation followed by 60–70 min hypoxia (8% oxygen). After HI, the pups recovered for 4 h under hypothermia (HI-TH group, n = 23) or normothermia (HI-N group, n = 23). Bilateral measurements of hemispheric CBFi were made with DCS in unanesthetized animals at baseline, before HI, and 0, 1, 2, 3, 4, 5, and 24 h after HI. The animals were sacrificed at either 1 or 4 weeks, and brain injury was scored on an ordinal scale of 0–5 (0 = no injury). Results Carotid ligation caused moderate bilateral decreases in CBFi. Following HI, an initial hyperemia was observed that was more prominent in the contralateral hemisphere. After initiation of TH, CBFi dropped significantly below baseline levels and remained reduced for the duration of TH. In contrast, CBFi in the HI-N group was not significantly decreased from baseline levels. Reductions in CBFi after 4 h of TH were not associated with reduced damage at 1 or 4 weeks. However, elevated ipsilateral CBFi and ipsilateral-to-contralateral CBFi ratios at 24 h were associated with worse outcome at 1 week after HI. Conclusions Both HI and TH alter CBFi, with significant differences in CBFi between

  18. Effect of two polyethylene covers in prevention of hypothermia among premature neonates

    PubMed Central

    Talakoub, Sedigheh; Shahbazifard, Zahra; Armanian, Amir Mohamad; Ghazavi, Zohreh

    2015-01-01

    Background: After the umbilical cord is cut, premature neonates face numerous problems including hypothermia. With regard to serious complications of hypothermia and incapability of conventional methods in preservation of neonates’ temperature after admission, the researcher decided to conduct a study on the effects of two polyethylene covers in prevention of hypothermia among premature neonates. Materials and Methods: This clinical trial was conducted on 96 neonates aged 28–32 weeks that randomly allocated, by drawing of lots, to three 32-subject groups as follows: Intervention group 1 (a plastic bag cover and a cotton hat), intervention group 2 (a plastic bag cover and a plastic hat), and a control group receiving routine care. Data were analyzed by descriptive and inferential statistics through SPSS V.14. Results: Mean axillary temperatures in intervention groups 1 and 2 were different after admission and 1 and 2 h later, but this difference was not significant and the mean axillary temperature increased with time. Mean axillary temperature in the control group showed no significant difference at these time points and it did not increase with time. The mean temperatures in preterm infants were significantly higher in the intervention groups after admission and 1 and 2 h after birth, compared to the control group. Mean axillary temperature in intervention group 2 was significantly higher than in intervention group 1. Conclusions: Usage of a plastic bag cover and a plastic hat (with no risk of hyperthermia) is more effective in preventing hypothermia among neonates aged 28–32 weeks, compared to usage of a plastic bag cover and a cotton hat. PMID:26120331

  19. Resection of the Aortic Arch with Moderate Hypothermia and Temporary Circulatory Arrest

    PubMed Central

    Speir, Alan M.; Grey, Douglas P.; Cooley, Denton A.

    1982-01-01

    Resection of the aortic arch with the use of moderate hypothermia and temporary circulatory arrest was performed in a 63-year-old woman. The simplified technique is described, along with a brief review of the literature. The patient recovered uneventfully. After this manuscript was prepared, two other patients underwent successful replacement of the aortic arch for aneurysm. These cases are also summarized briefly in an illustrated table. PMID:15226933

  20. Hypoxia, an adjunct in helium-cold hypothermia - Sparing effect on hepatic and cardiac metabolites.

    NASA Technical Reports Server (NTRS)

    Anderson, G. L.; Resch, G. E.; Musacchia, X. J.

    1973-01-01

    Investigation of the effect of hypoxia on the depletion of metabolites that occurs in helium-aided induction of hypothermia. Hypoxic slowing of the heart of a hamster while exposed to cold helox is demonstrated. An attempt is made to evaluate the relative importance of cardiac slowing and limitation of thermogenesis in determining the effect of hypoxia. In explanation of the results presented, it is suggested that hypoxia limits the energy expenditure by the heart during induction.

  1. Management of Super-Refractory Status Epilepticus with Isoflurane and Hypothermia

    PubMed Central

    Zhumadilov, Agzam; Gilman, Charles P.; Viderman, Dmitriy

    2015-01-01

    Super-refractory status epilepticus (SRSE) is defined as status epilepticus that continues 24 h or more after the onset of anesthesia, and includes those cases in which epilepsy is recurrent upon treatment reduction. We describe the presentation and successful management of a male patient with SRSE using the inhaled anesthetic isoflurane, and mild hypothermia (HT). The potential utility of combined HT and volatile anesthesia is discussed. PMID:25674075

  2. Radioprotection in depressed metabolic states: The physiology of helium-cold hypothermia

    NASA Technical Reports Server (NTRS)

    Musacchia, X. J.

    1973-01-01

    The use of hypothermia as a means of radiation protection was studied on a variety of mammals exposed to 80% helium-20% oxygen atmospheres at low ambient temperatures. Results show that the LD for normothermic animals significantly increased compared with hypothermic animals; similar results were obtained for hibernating mammalians. Pre-exposure of animals to cold temperatures increased their ability to withstand radiation levels close to LD sub 50.

  3. A tale of two climbers: hypothermia, death, and survival on Mount Everest.

    PubMed

    Moore, G W Kent; Semple, John L

    2012-03-01

    Hypothermia is an acknowledged risk for those who venture into high altitude regions. There is however little quantitative information on this risk that can be used to implement mitigation strategies. Here we provide an analysis of the meteorological and hypothermic risk parameters, wind chill temperature, and facial frostbite time, during the spring 2006 Mount Everest climbing season. This season was marked by two high profile events where a solo climber was forced to spend the night in highly exposed conditions near the summit. One climber survived, while the other did not. Although this retrospective examination of two individual cases has admittedly a small sample size, and there are other factors that undoubtedly contributed to the difference in outcomes, we show that wind chill temperature and facial frostbite time experienced by the two climbers were dramatically different. In particular, the climber who did not survive experienced conditions that were approximately one standard deviation more severe that usual for that time of the year; while the climber who survived experienced conditions that were approximately one standard deviation less severe then usual. This suggests that the environmental conditions associated with hypothermia played an important role in the outcomes. This report confirms the importance of providing quantitative guidance to climbers as the risk of hypothermia on high mountains. PMID:22429233

  4. Rewarming for accidental hypothermia in an urban medical center using extracorporeal membrane oxygenation

    PubMed Central

    Morley, David; Yamane, Kentaro; O’Malley, Rika; Cavarocchi, Nicholas C.; Hirose, Hitoshi

    2013-01-01

    Summary Background: Accidental hypothermia complicated by cardiac arrest carries a high mortality rate in urban areas. For moderate hypothermia cases conventional rewarming methods are usually adequate, however in severe cases extracorporeal membrane oxygenation (ECMO) is known to provide the most efficient rewarming with complete cardiopulmonary support. We report a case of severe hypothermia complicated by prolonged cardiac arrest successfully resuscitated using ECMO. Case Report: A 45 year old female was brought to our emergency department with a core body temperature <25°C. Shortly after arrival she had witnessed cardiac arrest in the department. Resuscitative efforts were started immediately including conventional rewarming techniques, followed by ECMO support. ECMO was used successfully in this case to resuscitate this patient from prolonged arrest (3.5 hours) when conventional techniques likely would have failed. After a prolonged hospital course this patient was discharged with her baseline mental and physical capacities intact. Conclusions: This case demonstrates the advantages of advanced internal rewarming techniques, such as ECMO, for quick and efficient rewarming of severely hypothermic patients. This case supports the use of ECMO in severely hypothermic patients as the standard of care. PMID:23569552

  5. Therapeutic hypothermia for acute ischemic stroke: ready to start large randomized trials?

    PubMed Central

    van der Worp, H Bart; Macleod, Malcolm R; Kollmar, Rainer

    2010-01-01

    Therapeutic hypothermia is a means of neuroprotection well established in the management of acute ischemic brain injuries such as anoxic encephalopathy after cardiac arrest and perinatal asphyxia. As such, it is the only neuroprotective strategy for which there is robust evidence for efficacy. Although there is overwhelming evidence from animal studies that cooling also improves outcome after focal cerebral ischemia, this has not been adequately tested in patients with acute ischemic stroke. There are still some uncertainties about crucial factors relating to the delivery of hypothermia, and the resolution of these would allow improvements in the design of phase III studies in these patients and improvements in the prospects for successful translation. In this study, we discuss critical issues relating first to the targets for therapy including the optimal depth and duration of cooling, second to practical issues including the methods of cooling and the management of shivering, and finally, of factors relating to the design of clinical trials. Consideration of these factors should inform the development of strategies to establish beyond doubt the place of hypothermia in the management of acute ischemic stroke. PMID:20354545

  6. Respiration during hypothermia: effect of rewarming intermediate areas of ventral medulla.

    PubMed

    Kiley, J P; Eldridge, F L; Millhorn, D E

    1985-11-01

    We studied respiration (phrenic nerve activity) during progressive hypothermia to as low as 30.5 degrees C in five anesthetized, paralyzed, glomectomized, and vagotomized cats. PCO2 was maintained at a constant level throughout the experiments. We confirmed the results of a previous study (J. P. Kiley, F. L. Eldridge, and D. E. Millhorn, J. Appl. Physiol. 58: 295-312, 1985) in which respiratory minute output decreased progressively with cooling and respiratory frequency decreased markedly. In addition we show that focal rewarming to normal temperature (37.5 degrees C) of the structures in the intermediate areas on the ventral surface of the medulla resulted in a significant reversal of the depressed respiratory minute activity observed with hypothermia. Respiratory frequency, however, was unaffected by intermediate area rewarming. We conclude that the decreased respiratory activity during hypothermia is due to a generalized interference with neural function. A major portion of these effects is due to cooling of the intermediate areas, but the slowing of respiratory frequency appears to be an independent effect. PMID:4066572

  7. Mild hypothermia inhibits systemic and cerebral complement activation in a swine model of cardiac arrest

    PubMed Central

    Gong, Ping; Zhao, Hong; Hua, Rong; Zhang, Mingyue; Tang, Ziren; Mei, Xue; Cui, Juan; Li, Chunsheng

    2015-01-01

    Complement activation has been implicated in ischemia/reperfusion injury. This study aimed to determine whether mild hypothermia (HT) inhibits systemic and cerebral complement activation after resuscitation from cardiac arrest. Sixteen minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were randomized into two groups: HT group (n=8), treated with HT (33°C) for 12 hours; and normothermia group (n=8), treated similarly as HT group except for cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). The brain cortex was harvested 24 hours after ROSC. Complement and pro-inflammatory markers were detected using enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24 hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a, interleukin-6, and tumor necrosis factor-α levels were significantly increased under normothermia within 24 hours after ROSC. However, these increases were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic outcome than normothermic pigs. In conclusion, complement is activated through classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic and cerebral complement activation, which may provide an additional mechanism of cerebral protection. PMID:25757755

  8. The ability of different thermal aids to reduce hypothermia in neonatal piglets.

    PubMed

    Pedersen, L J; Larsen, M L V; Malmkvist, J

    2016-05-01

    We investigated whether hypothermia in newborn piglets could be reduced by applying different thermal aids. The experiment was performed on 150 newborn piglets from 24 sows. Right after birth, the piglets were moved to a wire mesh cage for the first 2 h of life where they experienced 1 of 7 different combinations of flooring (solid vs. slatted) and treatments: control, with no additional thermal aids on a solid floor ( = 26) or a slatted floor ( = 26); built-in floor heating ( = 31) or floor heating as a radiant floor plate on solid floor (FloorPlate; = 19); radiant heater above a solid floor (RadiantC; = 22) or a slatted floor (RadiantSlat; = 18); and provision of straw on a solid floor (Straw; = 8). Piglets' rectal temperature was measured both continuously and manually every 10 min for the first 2 h after birth using a thermal sensor inserted in the rectum of the piglets. The rectal temperature curve was analyzed for differences in the slope of the drop in rectal temperature and the deflection tangent of the curve. Furthermore, differences in average rectal temperature, minimum rectal temperature, rectal temperature 2 h after birth, and time with rectal temperature below 35°C were analyzed. All statistical analyses were performed using a mixed model. All thermal aids/heat solutions resulted in a less steep drop in rectal temperature, a faster recovery, and, for the smaller piglets, also a greater average rectal temperature (except for built-in floor heating) and less time with rectal temperature below 35°C. The most efficient thermal aids to reduce hypothermia in newborn piglets were Straw and RadiantC. Furthermore, Straw, RadiantC, and FloorPlate also eliminated the effect of birth weight on some of these indicators of thermoregulatory success. Otherwise, FloorPlate and RadiantSlat showed an intermediate outcome for most measures. With no heating, piglets on a solid floor experienced more severe hypothermia than piglets on a slatted floor. In conclusion

  9. Therapeutic Hypothermia after Out-of-Hospital Cardiac Arrest in Children

    PubMed Central

    Moler, Frank W.; Silverstein, Faye S.; Holubkov, Richard; Slomine, Beth S.; Christensen, James R.; Nadkarni, Vinay M.; Meert, Kathleen L.; Clark, Amy E.; Browning, Brittan; Pemberton, Victoria L.; Page, Kent; Shankaran, Seetha; Hutchison, Jamie S.; Newth, Christopher J.L.; Bennett, Kimberly S.; Berger, John T.; Topjian, Alexis; Pineda, Jose A.; Koch, Joshua D.; Schleien, Charles L.; Dalton, Heidi J.; Ofori-Amanfo, George; Goodman, Denise M.; Fink, Ericka L.; McQuillen, Patrick; Zimmerman, Jerry J.; Thomas, Neal J.; van der Jagt, Elise W.; Porter, Melissa B.; Meyer, Michael T.; Harrison, Rick; Pham, Nga; Schwarz, Adam J.; Nowak, Jeffrey E.; Alten, Jeffrey; Wheeler, Derek S.; Bhalala, Utpal S.; Lidsky, Karen; Lloyd, Eric; Mathur, Mudit; Shah, Samir; Wu, Theodore; Theodorou, Andreas A.; Sanders, Ronald C.; Dean, J. Michael

    2015-01-01

    Background Therapeutic hypothermia is recommended for comatose adults after witnessed out-of-hospital cardiac arrest, but data about this intervention in children are limited. Methods We conducted this trial of two targeted temperature interventions at 38 children’s hospitals involving children who remained unconscious after out-of-hospital cardiac arrest. Within 6 hours after the return of circulation, comatose patients who were older than 2 days and younger than 18 years of age were randomly assigned to therapeutic hypothermia (target temperature, 33.0°C) or therapeutic normothermia (target temperature, 36.8°C). The primary efficacy outcome, survival at 12 months after cardiac arrest with a Vineland Adaptive Behavior Scales, second edition (VABS-II), score of 70 or higher (on a scale from 20 to 160, with higher scores indicating better function), was evaluated among patients with a VABS-II score of at least 70 before cardiac arrest. Results A total of 295 patients underwent randomization. Among the 260 patients with data that could be evaluated and who had a VABS-II score of at least 70 before cardiac arrest, there was no significant difference in the primary outcome between the hypothermia group and the normothermia group (20% vs. 12%; relative likelihood, 1.54; 95% confidence interval [CI], 0.86 to 2.76; P = 0.14). Among all the patients with data that could be evaluated, the change in the VABS-II score from baseline to 12 months was not significantly different (P = 0.13) and 1-year survival was similar (38% in the hypothermia group vs. 29% in the normothermia group; relative likelihood, 1.29; 95% CI, 0.93 to 1.79; P = 0.13). The groups had similar incidences of infection and serious arrhythmias, as well as similar use of blood products and 28-day mortality. Conclusions In comatose children who survived out-of-hospital cardiac arrest, therapeutic hypothermia, as compared with therapeutic normothermia, did not confer a significant benefit in survival with a

  10. Hypothermia Decreases Cerebrospinal Fluid Asymmetric Dimethylarginine Levels in Traumatic Brain Injury Children

    PubMed Central

    Thampatty, Bhavani P; Klamerus, Megan M; Oberly, Patrick J; Feldman, Kerri L; Bell, Michael J; Tyler-Kabara, Elizabeth C; Adelson, P. David; Clark, Robert SB; Kochanek, Patrick M; Poloyac, Samuel M

    2014-01-01

    Objectives Pathological increases in asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, have been implicated in endothelial dysfunction and vascular diseases. Reduced NO early after traumatic brain injury (TBI) may contribute to hypoperfusion. Currently, methods to quantify ADMA in the cerebrospinal fluid (CSF) have not been fully explored. We aimed to develop and validate a method to determine ADMA in the CSF of a pediatric TBI population and to use this method to assess the effects of (i) TBI and (ii) therapeutic hypothermia (TH) on this mediator. Design, Setting, Patients An ancillary study to a prospective, phase II randomized clinical trial (RCT) of early hypothermia in a tertiary care pediatric intensive care unit for children with TBI admitted to Children's Hospital of Pittsburgh. Interventions None Measurements and Main Results A UPLC-MS/MS method was developed and validated to quantitate ADMA. A total of 56 samples collected over 3 days starting with injury onset were analyzed from the CSF of consented therapeutic hypothermia (n=9) and normothermia (n=10) children. Children undergoing diagnostic lumbar puncture (n=5) were controls. ADMA was present at a quantifiable level in all samples. Mean ADMA levels were significantly increased in normothermic TBI children compared to control (0.19± 0.08 μmol/L and 0.11± 0.02μmol/L respectively, p=0.01), and hypothermic children had significantly reduced mean ADMA levels (0.11 ± 0.05 μmol/L) vs. normothermic (p=0.03) measured on day 3. Patient demographics including age, gender, and NO levels (measured as nitrite and nitrate using liquid chromatography coupled with Griess reaction) did not significantly differ between normothermia and hypothermia groups. Also, NO levels did not correlate with ADMA concentrations. Conclusions ADMA levels were significantly increased in the CSF of TBI children. Early hypothermia attenuated this increase. The implications of attenuated ADMA on

  11. The Effects of Local and General Hypothermia on Temperature Profiles of the Central Nervous System Following Spinal Cord Injury in Rats

    PubMed Central

    Bazley, Faith A.; Pashai, Nikta; Kerr, Candace L.

    2014-01-01

    Local and general hypothermia are used to treat spinal cord injury (SCI), as well as other neurological traumas. While hypothermia is known to provide significant therapeutic benefits due to its neuroprotective nature, it is unclear how the treatment may affect healthy tissues or whether it may cause undesired temperature changes in areas of the body that are not the targets of treatment. We performed 2-hour moderate general hypothermia (32°C core) or local hypothermia (30°C spinal cord) on rats that had received either a moderate contusive SCI or laminectomy (control) while monitoring temperatures at three sites: the core, spinal cord, and cortex. First, we identified that injured rats that received general hypothermia exhibited larger temperature drops at the spinal cord (−3.65°C, 95% confidence intervals [CIs] −3.72, −3.58) and cortex (−3.64°C, CIs −3.73, −3.55) than uninjured rats (spinal cord: −3.17°C, CIs −3.24, −3.10; cortex: −3.26°C, CIs −3.34, −3.17). This was found due to elevated baseline temperatures in the injured group, which could be due to inflammation. Second, both general hypothermia and local hypothermia caused a significant reduction in the cortical temperature (−3.64°C and −1.18°C, respectively), although local hypothermia caused a significantly lower drop in cortical temperature than general hypothermia (p<0.001). Lastly, the rates of rewarming of the cord were not significantly different among the methods or injury groups that were tested; the mean rate of rewarming was 0.13±0.1°C/min. In conclusion, local hypothermia may be more suitable for longer durations of hypothermia treatment for SCI to reduce temperature changes in healthy tissues, including the cortex. PMID:25019643

  12. Multiscale Entropy Analysis of EEG for Assessment of Post-Cardiac Arrest Neurological Recovery Under Hypothermia in Rats

    PubMed Central

    Kang, Xiaoxu; Jia, Xiaofeng; Geocadin, Romergryko G.; Maybhate, Anil

    2011-01-01

    Neurological complications after cardiac arrest (CA) can be fatal. Although hypothermia has been shown to be beneficial, understanding the mechanism and establishing neurological outcomes remains challenging because effects of CA and hypothermia are not well characterized. This paper aims to analyze EEG (and the α-rhythms) using multiscale entropy (MSE) to demonstrate the ability of MSE in tracking changes due to hypothermia and compare MSE during early recovery with long-term neurological examinations. Ten Wistar rats, upon post-CA resuscitation, were randomly subjected to hypothermia (32 °C–34 °C, N = 5) or normothermia (36.5 °C–37.5 °C, N = 5). EEG was recorded and analyzed using MSE during seven recovery phases for each experiment: baseline, CA, and five early recovery phases (R1–R5). Postresuscitation neurological examination was performed at 6, 24, 48, and 72 h to obtain neurological deficit scores (NDSs). Results showed MSE to be a sensitive marker of changes in α-rhythms. Significant difference (p < 0.05) was found between the MSE for two groups during recovery, suggesting that MSE can successfully reflect temperature modulation. A comparison of short-term MSE and long-term NDS suggested that MSE could be used for predicting favorability of long-term outcome. These experiments point to the role of cortical rhythms in reporting early neurological response to ischemia and therapeutic hypothermia. PMID:19174339

  13. Multiscale entropy analysis of EEG for assessment of post-cardiac arrest neurological recovery under hypothermia in rats.

    PubMed

    Kang, Xiaoxu; Jia, Xiaofeng; Geocadin, Romergryko G; Thakor, Nitish V; Maybhate, Anil

    2009-04-01

    Neurological complications after cardiac arrest (CA) can be fatal. Although hypothermia has been shown to be beneficial, understanding the mechanism and establishing neurological outcomes remains challenging because effects of CA and hypothermia are not well characterized. This paper aims to analyze EEG (and the alpha-rhythms) using multiscale entropy (MSE) to demonstrate the ability of MSE in tracking changes due to hypothermia and compare MSE during early recovery with long-term neurological examinations. Ten Wistar rats, upon post-CA resuscitation, were randomly subjected to hypothermia (32 degrees C-34 degrees C, N = 5) or normothermia (36.5 degrees C-37.5 degrees C, N = 5). EEG was recorded and analyzed using MSE during seven recovery phases for each experiment: baseline, CA, and five early recovery phases (R1-R5). Postresuscitation neurological examination was performed at 6, 24, 48, and 72 h to obtain neurological deficit scores (NDSs). Results showed MSE to be a sensitive marker of changes in alpha-rhythms. Significant difference (p < 0.05) was found between the MSE for two groups during recovery, suggesting that MSE can successfully reflect temperature modulation. A comparison of short-term MSE and long-term NDS suggested that MSE could be used for predicting favorability of long-term outcome. These experiments point to the role of cortical rhythms in reporting early neurological response to ischemia and therapeutic hypothermia. PMID:19174339

  14. Bleeding following deep hypothermia and circulatory arrest in children.

    PubMed

    Mossad, Emad B; Machado, Sandra; Apostolakis, John

    2007-03-01

    Deep hypothermic circulatory arrest (DHCA) is a technique of extracorporeal circulation commonly used in children with complex congenital heart defects undergoing surgical repairs. The use of profound cooling (20 degrees C) and complete cessation of circulation allow adequate exposure and correction of these complex lesions, with enhanced cerebral protection. However, the profound physiologic state of DHCA results in significant derangement of the coagulation system and a high incidence of postoperative bleeding. This review examines the impact of DHCA on bleeding and transfusion requirements in children and the pathophysiology of DHCA-induced platelet dysfunction. It also focuses on possible pharmacologic interventions to decrease bleeding following DHCA in children. PMID:17484172

  15. Perinatal risk factors for severe injury in neonates treated with whole-body hypothermia for encephalopathy

    PubMed Central

    Wayock, Christopher P.; Meserole, Rachel L.; Saria, Suchi; Jennings, Jacky M.; Huisman, Thierry A. G. M.; Northington, Frances J.; Graham, Ernest M.

    2016-01-01

    Objective Our objective was to identify perinatal risk factors that are available within 1 hour of birth that are associated with severe brain injury after hypothermia treatment for suspected hypoxic-ischemic encephalopathy. Study Design One hundred nine neonates at ≥35 weeks' gestation who were admitted from January 2007 to September 2012 with suspected hypoxic-ischemic encephalopathy were treated with whole-body hypothermia; 98 of them (90%) underwent brain magnetic resonance imaging (MRI) at 7-10 days of life. Eight neonates died before brain imaging. Neonates who had severe brain injury, which was defined as death or abnormal MRI results (cases), were compared with surviving neonates with normal MRI (control subjects). Logistic regression models were used to identify risk factors that were predictive of severe injury. Results Cases and control subjects did not differ with regard to gestational age, birthweight, mode of delivery, or diagnosis of non-reassuring fetal heart rate before delivery. Cases were significantly (P ≤ .05) more likely to have had an abruption, a cord and neonatal arterial gas level that showed metabolic acidosis, lower platelet counts, lower glucose level, longer time to spontaneous respirations, intubation, chest compressions in the delivery room, and seizures. In multivariable logistic regression, lower initial neonatal arterial pH (P = .004), spontaneous respiration at >30 minutes of life (P = .002), and absence of exposure to oxytocin (P = .033) were associated independently with severe injury with 74.3% sensitivity and 74.4% specificity. Conclusion Worsening metabolic acidosis at birth, longer time to spontaneous respirations, and lack of exposure to oxytocin correlated with severe brain injury in neonates who were treated with whole-body hypothermia. These risk factors may help quickly identify neonatal candidates for time-sensitive investigational therapies for brain neuroprotection. PMID:24657795

  16. Early Absent Pupillary Light Reflexes After Cardiac Arrest in Patients Treated with Therapeutic Hypothermia.

    PubMed

    Dhakal, Laxmi P; Sen, Ayan; Stanko, Carlene M; Rawal, Bhupendra; Heckman, Michael G; Hoyne, Jonathan B; Dimberg, Elliot L; Freeman, Michelle L; Ng, Lauren K; Rabinstein, Alejandro A; Freeman, William D

    2016-08-01

    Loss of pupillary light reactivity is one recognized indicator of poor prognosis after cardiopulmonary resuscitation (CPR). However, drug overdose, low cardiac output, and/or resuscitation drugs can lead to impaired pupillary light reflex. To investigate pupillary light reflex status before therapeutic hypothermia (TH) in relation to neurological outcome, we retrospectively reviewed the data of a prospectively implemented TH protocol in patients with cardiac arrest (CA) at Mayo Clinic in Jacksonville, Florida (January 2006-January 2012), and Mayo Clinic in Scottsdale, Arizona (August 2010-March 2014). During this period, all CA patients who underwent hypothermia were included. These patients were selected from an institutional database and hypothermia data set. The Cerebral Performance Category (CPC) at time of discharge was our primary outcome measure. A CPC of 1 to 2 was defined as good outcome and a CPC from 3 to 5 was defined as poor outcome. We identified 99 patients who had CA treated with TH. Twenty-nine patients (29%) had pupils that were nonreactive to light on admission examination before TH, eight of whom later had return of pupil reactivity by day 3. Two of these 29 patients (6.9%) had good outcome, compared to 24 of 70 patients (34.3%) with pupils that were reactive to light (p = 0.005). Both of these patients had CA after illicit drug overdose. Early nonreactive pupils occurred in almost a third of patients after CPR and before TH in our patient population. Recovery of pupillary light reactivity is possible, and in a small minority of those cases (particularly when CA is preceded by the use of illicit drugs), a good outcome can be achieved. PMID:27135180

  17. Effects of prehospital hypothermia on transfusion requirements and outcomes: a retrospective observatory trial

    PubMed Central

    Klauke, Nora; Gräff, Ingo; Fleischer, Andreas; Boehm, Olaf; Guttenthaler, Vera; Baumgarten, Georg; Meybohm, Patrick; Wittmann, Maria

    2016-01-01

    Objectives Prehospital hypothermia is defined as a core temperature <36.0°C and has been shown to be an independent risk factor for early death in patients with trauma. In a retrospective study, a possible correlation between the body temperature at the time of admission to the emergency room and subsequent in-hospital transfusion requirements and the in-hospital mortality rate was explored. Setting This is a retrospective single-centre study at a primary care hospital in Germany. Participants 15 895 patients were included in this study. Patients were classified by admission temperature and transfusion rate. Excluded were ambulant patients and patients with missing data. Primary and secondary outcome measures The primary outcome values were length of stay (LOS) in days, in-hospital mortality, the transferred amount of packed red blood cells (PRBCs), and admission to an intensive care unit. Secondary influencing variables were the patient's age and the Glasgow Coma Scale. Results In 22.85% of the patients, hypothermia was documented. Hypothermic patients died earlier in the course of their hospital stay than non-hypothermic patients (p<0.001). The administration of 1–3 PRBC increased the LOS significantly (p<0.001) and transfused patients had an increased risk of death (p<0.001). Prehospital hypothermia could be an independent risk factor for mortality (adjusted OR 8.521; p=0.001) and increases the relative risk for transfusion by factor 2.0 (OR 2.007; p=0.002). Conclusions Low body temperature at hospital admission is associated with a higher risk of transfusion and death. Hence, a greater awareness of prehospital temperature management should be established. PMID:27029772

  18. Comparison of three different prehospital wrapping methods for preventing hypothermia - a crossover study in humans

    PubMed Central

    2011-01-01

    Background Accidental hypothermia increases mortality and morbidity in trauma patients. Various methods for insulating and wrapping hypothermic patients are used worldwide. The aim of this study was to compare the thermal insulating effects and comfort of bubble wrap, ambulance blankets / quilts, and Hibler's method, a low-cost method combining a plastic outer layer with an insulating layer. Methods Eight volunteers were dressed in moistened clothing, exposed to a cold and windy environment then wrapped using one of the three different insulation methods in random order on three different days. They were rested quietly on their back for 60 minutes in a cold climatic chamber. Skin temperature, rectal temperature, oxygen consumption were measured, and metabolic heat production was calculated. A questionnaire was used for a subjective evaluation of comfort, thermal sensation, and shivering. Results Skin temperature was significantly higher 15 minutes after wrapping using Hibler's method compared with wrapping with ambulance blankets / quilts or bubble wrap. There were no differences in core temperature between the three insulating methods. The subjects reported more shivering, they felt colder, were more uncomfortable, and had an increased heat production when using bubble wrap compared with the other two methods. Hibler's method was the volunteers preferred method for preventing hypothermia. Bubble wrap was the least effective insulating method, and seemed to require significantly higher heat production to compensate for increased heat loss. Conclusions This study demonstrated that a combination of vapour tight layer and an additional dry insulating layer (Hibler's method) is the most efficient wrapping method to prevent heat loss, as shown by increased skin temperatures, lower metabolic rate and better thermal comfort. This should then be the method of choice when wrapping a wet patient at risk of developing hypothermia in prehospital environments. PMID:21699720

  19. Plastic Bags for Prevention of Hypothermia in Preterm and Low Birth Weight Infants

    PubMed Central

    Leadford, Alicia E.; Warren, Jamie B.; Manasyan, Albert; Chomba, Elwyn; Salas, Ariel A.; Schelonka, Robert

    2013-01-01

    BACKGROUND AND OBJECTIVES: Hypothermia contributes to neonatal mortality and morbidity, especially in preterm and low birth weight infants in developing countries. Plastic bags covering the trunk and extremities of very low birth weight infants reduces hypothermia. This technique has not been studied in larger infants or in many resource-limited settings. The objective was to determine if placing preterm and low birth weight infants inside a plastic bag at birth maintains normothermia. METHODS: Infants at 26 to 36 weeks’ gestational age and/or with a birth weight of 1000 to 2500 g born at the University Teaching Hospital in Lusaka, Zambia, were randomized by using a 1:1 allocation and parallel design to standard thermoregulation (blanket or radiant warmer) care or to standard thermoregulation care plus placement inside a plastic bag at birth. The primary outcome measure was axillary temperature in the World Health Organization–defined normal range (36.5–37.5°C) at 1 hour after birth. RESULTS: A total of 104 infants were randomized. At 1 hour after birth, infants randomized to plastic bag (n = 49) were more likely to have a temperature in the normal range as compared with infants in the standard thermoregulation care group (n = 55; 59.2% vs 32.7%; relative risk 1.81; 95% confidence interval 1.16–2.81; P = .007). The temperature at 1 hour after birth in the infants randomized to plastic bag was 36.5 ± 0.5°C compared with 36.1 ± 0.6°C in standard care infants (P < .001). Hyperthermia (>38.0°C) did not occur in any infant. CONCLUSIONS: Placement of preterm/low birth weight infants inside a plastic bag at birth compared with standard thermoregulation care reduced hypothermia without resulting in hyperthermia, and is a low-cost, low-technology tool for resource-limited settings. PMID:23733796

  20. HYPOTHERMIA AND VALPROIC ACID ACTIVATE PRO-SURVIVAL PATHWAYS AFTER HEMORRHAGE

    PubMed Central

    Bambakidis, Ted; Dekker, Simone E.; Liu, Baoling; Maxwell, Jake; Chatraklin, Kiril; Linzel, Durk; Li, Yongqing; Alam, Hasan B.

    2015-01-01

    Background Therapeutic hypothermia (Hypo) and valproic acid (VPA, a histone deacetylase inhibitor) have independently been shown to be protective in models of trauma and hemorrhagic shock (HS), but require logistically challenging doses to be effective. Theoretically, combined treatment may further enhance effectiveness, allowing us to use lower doses of each modality. The aim of this study was to determine whether a combination of mild hypothermia and VPA treatments would offer better cytoprotection compared to individual treatments in a hemorrhage model. Materials and methods Male Sprague-Dawley rats were subjected to 40% volume-controlled hemorrhage, kept in shock for 30 minutes, and assigned to one of the following treatment groups: normothermia (36–37°C), Hypo (30±2°C), normothermia+VPA (300mg/kg), and Hypo+VPA (n=5/group). After three hours of observation, the animals were sacrificed, liver tissue was harvested and subjected to whole cell lysis, and levels of key proteins in the pro-survival Akt pathway were measured using Western Blot. Results Activation of the pro-apoptotic protein cleaved-caspase-3 was significantly lower in the combined treatment group relative to normothermia (P<0.05). Levels of the pro-survival Bcl-2 was significantly higher in the combined treatment group relative to sham, normothermia, and normothermia+VPA groups (P<0.005). The downstream pro-survival protein phospho-GSK-3β was significantly higher in the sham, Hypo, and combined treatment groups compared to normothermia groups with or without VPA (P<0.05). Levels of the pro-survival β-catenin were significantly higher in the combined treatment group relative to normothermia (P<0.01). Conclusions This is the first in-vivo study to demonstrate that combined treatment with VPA and hypothermia offers better cytoprotection than these treatments given independently. PMID:25777823

  1. Capillary leakage in post-cardiac arrest survivors during therapeutic hypothermia - a prospective, randomised study

    PubMed Central

    2010-01-01

    Background Fluids are often given liberally after the return of spontaneous circulation. However, the optimal fluid regimen in survivors of cardiac arrest is unknown. Recent studies indicate an increased fluid requirement in post-cardiac arrest patients. During hypothermia, animal studies report extravasation in several organs, including the brain. We investigated two fluid strategies to determine whether the choice of fluid would influence fluid requirements, capillary leakage and oedema formation. Methods 19 survivors with witnessed cardiac arrest of primary cardiac origin were allocated to either 7.2% hypertonic saline with 6% poly (O-2-hydroxyethyl) starch solution (HH) or standard fluid therapy (Ringer's Acetate and saline 9 mg/ml) (control). The patients were treated with the randomised fluid immediately after admission and continued for 24 hours of therapeutic hypothermia. Results During the first 24 hours, the HH patients required significantly less i.v. fluid than the control patients (4750 ml versus 8010 ml, p = 0.019) with comparable use of vasopressors. Systemic vascular resistance was significantly reduced from 0 to 24 hours (p = 0.014), with no difference between the groups. Colloid osmotic pressure (COP) in serum and interstitial fluid (p < 0.001 and p = 0.014 respectively) decreased as a function of time in both groups, with a more pronounced reduction in interstitial COP in the crystalloid group. Magnetic resonance imaging of the brain did not reveal vasogenic oedema. Conclusions Post-cardiac arrest patients have high fluid requirements during therapeutic hypothermia, probably due to increased extravasation. The use of HH reduced the fluid requirement significantly. However, the lack of brain oedema in both groups suggests no superior fluid regimen. Cardiac index was significantly improved in the group treated with crystalloids. Although we do not associate HH with the renal failures that developed, caution should be taken when using hypertonic

  2. Hypothermia Severely Effects Performance of Nitinol-Based Endovascular Grafts In Vitro

    PubMed Central

    Robich, Michael P.; Hagberg, Robert; Schermerhorn, Marc L.; Pomposelli, Frank B.; Nilson, Michael C.; Gendron, Michelle L.; Sellke, Frank W.; Rodriguez, Roberto

    2012-01-01

    Background Nitinol is an alloy that serves as the base for numerous medical devices, including the GORE TAG Thoracic Endoprosthesis (W.L. Gore & Associates, Flagstaff, AZ) thoracic aortic graft device. Given the increasing use of therapeutic hypothermia used during the placement these devices and in post– cardiac arrest situations, we sought to understand the impact of hypothermia on this device. Methods Five 34-mm TAG devices were deployed in a temperature-controlled chamber at 20°C, 25°C, 30°C, 35°, and 37°C (25 total devices). A halographic measurement device was used to measure radial expansive force and normalized to the force at 37°C. Three 34-mm TAG devices were similarly deployed in a temperature-controlled water bath at each of the above temperatures. A laser micrometer was utilized to measure deployed diameter. Results A statistically significant decrease in expansive force at 20°C, 25°C, and 30°C of 65%, 46%, and 6%, respectively, was noted. A statistically significant decrease in radial diameter at 20°C and 25°C of 17% and 11%, respectively, was noted. Although a 9% difference was noted at 30°C, it was not significant. Conclusions The nitinol-based TAG device shows marked decreases in radial expansive force and deployed diameter at temperatures at or below 30°C. Surgeons should be aware of the potential implications of placing nitinol-based endoprostheses in hypothermic conditions. In addition, all health care providers should be aware of the changes that occur in nitinol-based endoprostheses during therapeutic hypothermia. PMID:22385821

  3. Combined Neuroprotective Modalities Coupled with Thrombolysis in Acute Ischemic Stroke: A Pilot Study of Caffeinol and Mild Hypothermia

    PubMed Central

    Martin-Schild, Sheryl; Hallevi, Hen; Shaltoni, Hashem; Barreto, Andrew D.; Gonzales, Nicole R.; Aronowski, Jarek; Savitz, Sean I.; Grotta, James C.

    2009-01-01

    Background Both caffeinol and hypothermia are neuroprotective in preclinical models of transient middle cerebral artery occlusion. We tested whether combining caffeinol and hypothermia with t-PA in acute stroke patients is safe and feasible. Methods 20 patients with acute ischemic stroke were treated with caffeinol (caffeine 8-9 mg/kg + ethanol 0.4g/kg IV X 2 hours, started by 4 hrs after symptom onset) and hypothermia (started by 5 hrs and continued for 24 hrs (target temp 33-35°C) followed by 12 hrs of rewarming). IV t-PA was given to eligible patients. Meperidine and buspirone were used to suppress shivering. Results All patients received caffeinol, and most reached target blood levels. Cooling was attempted in 18 patients via endovascular (n=8) or surface (n=10) approaches. Two patients were not cooled due to catheter or machine failure. Thirteen patients reached target temperature; average time from symptom onset was 9hrs, 43min. The last 5 hypothermia patients received surface cooling with iced saline induction and larger doses of meperidine; all patients reached target temperature, on average within 2hrs 30min from induction and 6hrs 21min from symptom onset. Three patients died: one from symptomatic hemorrhage, one from malignant cerebral edema, and one from unrelated medical complications. No adverse events were attributed to caffeinol. One patient had reduced respiratory drive due to meperidine, requiring BiPAP. Discussion Combining caffeinol with hypothermia in acute stroke patients given IV t-PA is feasible. A prospective placebo-controlled randomized study is needed to further assess safety and to test the efficacy of caffeinol, hypothermia or both. PMID:19251183

  4. Intracranial Pressure Elevation 24 h after Ischemic Stroke in Aged Rats Is Prevented by Early, Short Hypothermia Treatment

    PubMed Central

    Murtha, Lucy A.; Beard, Daniel J.; Bourke, Julia T.; Pepperall, Debbie; McLeod, Damian D.; Spratt, Neil J.

    2016-01-01

    Stroke is predominantly a senescent disease, yet most preclinical studies investigate treatment in young animals. We recently demonstrated that short-duration hypothermia-treatment completely prevented the dramatic intracranial pressure (ICP) rise seen post-stroke in young rats. Here, our aim was to investigate whether a similar ICP rise occurs in aged rats and to determine whether short-duration hypothermia is an effective treatment in aged animals. Experimental middle cerebral artery occlusion (MCAo-3 h occlusion) was performed on male Wistar rats aged 19–20 months. At 1 h after stroke-onset, rats were randomized to 2.5 h hypothermia-treatment (32.5°C) or normothermia (37°C). ICP was monitored at baseline, for 3.5 h post-occlusion, and at 24 h post-stroke. Infarct and edema volumes were calculated from histology. Baseline pre-stroke ICP was 11.2 ± 3.3 mmHg across all animals. Twenty-four hours post-stroke, ICP was significantly higher in normothermic animals compared to hypothermia-treated animals (27.4 ± 18.2 mmHg vs. 8.0 ± 5.0 mmHg, p = 0.03). Infarct and edema volumes were not significantly different between groups. These data demonstrate ICP may also increase 24 h post-stroke in aged rats, and that short-duration hypothermia treatment has a profound and sustained preventative effect. These findings may have important implications for the use of hypothermia in clinical trials of aged stroke patients. PMID:27303291

  5. Dominique-Jean Larrey: the effects of therapeutic hypothermia and the first ambulance.

    PubMed

    Remba, Salomon Jasqui; Varon, Joseph; Rivera, Alma; Sternbach, George L

    2010-03-01

    The fields of emergency medicine and resuscitation are indebted to the Baron Dominique-Jean Larrey (1766-1842) for significant advances in patient care. Larrey was a great surgeon who served in the French army during Napoleon's rule. He developed one of the first ambulance services, utilized positive pressure ventilation, and introduced hypothermia as a form of therapy. He dedicated his professional life to improving the care of wounded soldiers on the battlefield. Larrey coined the term "Triage" to allocate resources to those most in need of emergent care. Today, many of his techniques still prevail in modern medicine. PMID:20036046

  6. Platelet inhibition with prasugrel in patients with acute myocardial infarction undergoing therapeutic hypothermia after cardiopulmonary resuscitation.

    PubMed

    Flierl, Ulrike; Röntgen, Philipp; Zauner, Florian; Tongers, Jörn; Berliner, Dominik; Bauersachs, Johann; Schäfer, Andreas

    2016-05-01

    Acute myocardial infarction (AMI) is the leading cause for out-of-hospital cardiac arrest. Therapeutic hypothermia improves neurological outcome in combination with early revascularisation, but seems to affect clopidogrel responsiveness. The more potent thienopyridine prasugrel has not yet been sufficiently evaluated during therapeutic hypothermia. We investigated 23 consecutive AMI patients (61 ± 11 years) following out-of-hospital resuscitation undergoing revascularisation and therapeutic hypothermia. Prasugrel efficacy was assessed by the platelet-reactivity-index (PRI) before and 2, 4, 6, 12, 24, 48, and 72 hours (h) following a loading dose of 60 mg via a gastric tube. Mean PRI (± SD) was 70 ± 12 % prior to loading and 60 ± 16 % (2 h, ns), 52 ± 21 % (4 h, p< 0.01), 42 ± 26 % (6 h, p< 0.01), 37 ± 21 % (12 h, p< 0.01), 27 ± 23 % (24 h, p< 0.01), 18 ± 14 % (48 h, p< 0.01), and 13 ± 10 % (72 h, p< 0.01) after loading. Sufficient platelet inhibition occurred later compared to stable AMI patients (6 h vs 2 h); however, high on-treatment platelet reactivity significantly decreased over time and was non-existent after 72 h (PRI> 50 %: 2 h: 72 %, 4 h: 52 %, 6 h: 43 %, 12 h: 29 %, 24 h: 17 %, 48 h: 5 %, 72 h: 0 %). There was no relation between 30-day mortality rate (26 %) and PRI values. Prasugrel significantly reduced platelet reactivity even during vasopressor use, analgosedation and therapeutic hypothermia. Despite a significant delay compared to stable AMI patients, sufficient platelet inhibition was reached in 83 % of patients within 24 h. Therefore, prasugrel administration via gastric tube might be a useful therapeutic strategy in these patients at high risk, providing potent and effective P2Y12 inhibition. PMID:26790884

  7. Coronary artery bypass grafting in cold-induced urticaria.

    PubMed

    Bakay, Cihat; Onan, Burak; Onan, Ismihan Selen; Ozkara, Ahmet

    2010-03-01

    Cold-induced urticaria is an unusual systemic disorder that develops in response to exposures to cold temperatures in susceptible individuals. Patients with cold urticaria are potentially at risk of severe systemic anaphylactic shock-like reactions. This disorder is of unique clinical importance in cardiac surgery, considering the use of cardiopulmonary bypass and hypothermia. Contact of blood with hypothermia and subsequent warming can be associated with hemodynamic instability, hypotension, and cardiovascular collapse, mainly during the period of rewarming. We report the case of a 41-year-old woman with chronic cold-induced urticaria, who underwent a successful coronary bypass grafting, and describe perioperative management of this rare disorder. PMID:20172161

  8. Incidence of Inadvertent Intraoperative Hypothermia and Its Risk Factors in Patients Undergoing General Anesthesia in Beijing: A Prospective Regional Survey

    PubMed Central

    Deng, Xiaoming; Fan, Ting; Fu, Runqiao; Geng, Wanming; Guo, Ruihong; He, Nong; Li, Chenghui; Li, Lei; Li, Min; Li, Tianzuo; Tian, Ming; Wang, Geng; Wang, Lei; Wang, Tianlong; Wu, Anshi; Wu, Di; Xue, Xiaodong; Xu, Mingjun; Yang, Xiaoming; Yang, Zhanmin; Yuan, Jianhu; Zhao, Qiuhua; Zhou, Guoqing; Zuo, Mingzhang; Pan, Shuang; Zhan, Lujing; Yao, Min; Huang, Yuguang

    2015-01-01

    Background/Objective Inadvertent intraoperative hypothermia (core temperature <360 C) is a recognized risk in surgery and has adverse consequences. However, no data about this complication in China are available. Our study aimed to determine the incidence of inadvertent intraoperative hypothermia and its associated risk factors in a sample of Chinese patients. Methods We conducted a regional cross-sectional survey in Beijing from August through December, 2013. Eight hundred thirty patients who underwent various operations under general anesthesia were randomly selected from 24 hospitals through a multistage probability sampling. Multivariate logistic regression analyses were applied to explore the risk factors of developing hypothermia. Results The overall incidence of intraoperative hypothermia was high, 39.9%. All patients were warmed passively with surgical sheets or cotton blankets, whereas only 10.7% of patients received active warming with space heaters or electric blankets. Pre-warmed intravenous fluid were administered to 16.9% of patients, and 34.6% of patients had irrigation of wounds with pre-warmed fluid. Active warming (OR = 0.46, 95% CI 0.26–0.81), overweight or obesity (OR = 0.39, 95% CI 0.28–0.56), high baseline core temperature before anesthesia (OR = 0.08, 95% CI 0.04–0.13), and high ambient temperature (OR = 0.89, 95% CI 0.79–0.98) were significant protective factors for hypothermia. In contrast, major-plus operations (OR = 2.00, 95% CI 1.32–3.04), duration of anesthesia (1–2 h) (OR = 3.23, 95% CI 2.19–4.78) and >2 h (OR = 3.44, 95% CI 1.90–6.22,), and intravenous un-warmed fluid (OR = 2.45, 95% CI 1.45–4.12) significantly increased the risk of hypothermia. Conclusions The incidence of inadvertent intraoperative hypothermia in Beijing is high, and the rate of active warming of patients during operation is low. Concern for the development of intraoperative hypothermia should be especially high in patients undergoing major

  9. Wilderness Medical Society practice guidelines for the out-of-hospital evaluation and treatment of accidental hypothermia.

    PubMed

    Zafren, Ken; Giesbrecht, Gordon G; Danzl, Daniel F; Brugger, Hermann; Sagalyn, Emily B; Walpoth, Beat; Weiss, Eric A; Auerbach, Paul S; McIntosh, Scott E; Némethy, Mária; McDevitt, Marion; Dow, Jennifer; Schoene, Robert B; Rodway, George W; Hackett, Peter H; Bennett, Brad L; Grissom, Colin K

    2014-12-01

    To provide guidance to clinicians, the Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the out-of-hospital evaluation and treatment of victims of accidental hypothermia. The guidelines present the main diagnostic and therapeutic modalities and provide recommendations for the management of hypothermic patients. The panel graded the recommendations based on the quality of supporting evidence and the balance between benefits and risks/burdens according the criteria published by the American College of Chest Physicians. The guidelines also provide suggested general approaches to the evaluation and treatment of accidental hypothermia that incorporate specific recommendations. PMID:25443771

  10. 13C NMR Metabolomic Evaluation of Immediate and Delayed Mild Hypothermia in Cerebrocortical Slices After Oxygen-Glucose Deprivation

    PubMed Central

    Liu, Jia; Segal, Mark; Kelly, Mark J.S.; Pelton, Jeffrey G.; Kim, Myungwon; James, Thomas L.; Litt, Lawrence

    2013-01-01

    Background Mild brain hypothermia (32°C–34°C) after human neonatal asphyxia improves neurodevelopmental outcomes. Astrocytes but not neurons have pyruvate carboxylase (PC) and an acetate uptake transporter. 13C NMR spectroscopy of rodent brain extracts after administering [1-13C]glucose and [1,2-13C]acetate can distinguish metabolic differences between glia and neurons, and tricarboxylic acid cycle (TCA cycle) entry via pyruvate dehydrogenase (PDH) and PC. Methods Neonatal rat cerebrocortical slices receiving a 13C-acetate/glucose mixture underwent a 45-min asphyxia simulation via oxygen-glucose-deprivation (OGD) followed by 6 h of recovery. Protocols in three groups of N = 3 experiments were identical except for temperature management. The three temperature groups were: normothermia (37°C), hypothermia (32°C for 3.75 h beginning at OGD start), and delayed hypothermia (32°C for 3.75 h, beginning 15 min after OGD start). Multivariate analysis of nuclear magnetic resonance metabolite quantifications included principal component analyses and the L1-Penalized Regularized Regression algorithm known as the Least Absolute Shrinkage and Selection Operator (LASSO). Results The most significant metabolite difference (p < 0.0056) was [2-13C]glutamine’s higher final/control ratio for the Hypothermia group (1.75 ± 0.12) compared to ratios for the Delayed (1.12 ± 0.12) and Normothermia group (0.94 ± 0.06), implying a higher PC/PDH ratio for glutamine formation. LASSO found the most important metabolites associated with adenosine triphosphate preservation: [3,4-13C]glutamate—produced via PDH entry, [2-13C]taurine--an important osmolyte, and phosphocreatine. Final principal component analyses scores plots suggested separate cluster formation for the hypothermia group, but with insufficient data for statistical significance. Conclusions Starting mild hypothermia simultaneously with OGD, compared with delayed starting or no hypothermia, has higher PC throughput

  11. Combination therapy of normobaric oxygen with hypothermia or ethanol modulates pyruvate dehydrogenase complex in thromboembolic cerebral ischemia.

    PubMed

    Cai, Lipeng; Thibodeau, Alexa; Peng, Changya; Ji, Xunming; Rastogi, Radhika; Xin, Ruiqiang; Singh, Sunpreet; Geng, Xiaokun; Rafols, Jose A; Ding, Yuchuan

    2016-08-01

    Pyruvate dehydrogenase complex (PDH) is a brain mitochondrial matrix enzyme. PDH impairment after stroke is particularly devastating given PDH's critical role in the link between anaerobic and aerobic metabolism. This study evaluates the restoration of oxidative metabolism and energy regulation with a therapeutic combination of normobaric oxygen (NBO) plus either therapeutic hypothermia (TH) or ethanol. Sprague-Dawley rats were subjected to middle cerebral artery occlusion with an autologous embolus. One hour after occlusion, tissue-type plasminogen activator (t-PA) was administered alone or with NBO (60%), EtOH (1.0 g/kg), or TH (33°C), either singly or in combination. Neurological deficit score and infarct volume were assessed 24 hr after t-PA-induced reperfusion. PDH activity and reactive oxygen species (ROS) levels were measured 3 and 24 hr after t-PA. Western blotting was used to detect PDH and pyruvate dehydrogenase kinase (PDK) protein expression. After t-PA in ischemic rats, NBO combined with TH or EtOH most effectively decreased infarct volume and neurological deficit. The combined therapies produced greater increases in PDH activity and protein expression as well as greater decreases in PDK expression. Compared with the monotherapeutic approaches, the combined therapies provided the most significant declines in ROS generation. Reperfusion with t-PA followed by 60% NBO improves the efficacy of EtOH or TH in neuroprotection by ameliorating oxidative injury and improving PDH regulation. Comparable neuroprotective effects were found when treating with either EtOH or TH, suggesting a similar mechanism of neuroprotection and the possibility of substituting EtOH for TH in clinical settings. © 2016 Wiley Periodicals, Inc. PMID:27027410

  12. Body temperature changes during simulated bacterial infection in a songbird: fever at night and hypothermia during the day.

    PubMed

    Sköld-Chiriac, Sandra; Nord, Andreas; Tobler, Michael; Nilsson, Jan-Åke; Hasselquist, Dennis

    2015-09-01

    Although fever (a closely regulated increase in body temperature in response to infection) typically is beneficial, it is energetically costly and may induce detrimentally high body temperatures. This can increase the susceptibility to energetic bottlenecks and risks of overheating in some organisms. Accordingly, it could be particularly interesting to study fever in small birds, which have comparatively high metabolic rates and high, variable body temperatures. We therefore investigated two aspects of fever and other sickness behaviours (circadian variation, dose dependence) in a small songbird, the zebra finch. We injected lipopolysaccharide (LPS) at the beginning of either the day or the night, and subsequently monitored body temperature, body mass change and food intake for the duration of the response. We found pronounced circadian variation in the body temperature response to LPS injection, manifested by (dose-dependent) hypothermia during the day but fever at night. This resulted in body temperature during the peak response being relatively similar during the day and night. Day-to-night differences might be explained in the context of circadian variation in body temperature: songbirds have a high daytime body temperature that is augmented by substantial heat production peaks during activity. This might require a trade-off between the benefit of fever and the risk of overheating. In contrast, at night, when body temperature is typically lower and less variable, fever can be used to mitigate infection. We suggest that the change in body temperature during infection in small songbirds is context dependent and regulated to promote survival according to individual demands at the time of infection. PMID:26232416

  13. Dexmedetomidine Reduces Shivering during Mild Hypothermia in Waking Subjects

    PubMed Central

    Callaway, Clifton W.; Elmer, Jonathan; Guyette, Francis X.; Molyneaux, Bradley J.; Anderson, Kacey B.; Empey, Philip E.; Gerstel, Stacy J.; Holquist, Kate; Repine, Melissa J.; Rittenberger, Jon C.

    2015-01-01

    Background and Purpose Reducing body temperature can prolong tolerance to ischemic injury such as stroke or myocardial infarction, but is difficult and uncomfortable in awake patients because of shivering. We tested the efficacy and safety of the alpha-2-adrenergic agonist dexmedetomidine for suppressing shivering induced by a rapid infusion of cold intravenous fluids. Methods Ten subjects received a rapid intravenous infusion of two liters of cold (4°C) isotonic saline on two separate test days, and we measured their core body temperature, shivering, hemodynamics and sedation for two hours. On one test day, fluid infusion was preceded by placebo infusion. On the other test day, fluid infusion was preceded by 1.0 μg/kg bolus of dexmedetomidine over 10 minutes. Results All ten subjects experienced shivering on placebo days, with shivering beginning at a mean (SD) temperature of 36.6 (0.3)°C. The mean lowest temperature after placebo was 36.0 (0.3)°C (range 35.7-36.5°C). Only 3/10 subjects shivered on dexmedetomidine days, and the mean lowest temperature was 35.7 (0.4)°C (range 35.0-36.3°C). Temperature remained below 36°C for the full two hours in 6/10 subjects. After dexmedetomidine, subjects had moderate sedation and a mean 26 (13) mmHg reduction in blood pressure that resolved within 90 minutes. Heart rate declined a mean 23 (11) bpm after both placebo and dexmedetomidine. Dexmedetomidine produced no respiratory depression. Conclusion Dexmedetomidine decreases shivering in normal volunteers. This effect is associated with decreased systolic blood pressure and sedation, but no respiratory depression. PMID:26237219

  14. Effect of ethyl alcohol on thermoregulation in mice following the induction of hypothermia or hyperthermia.

    PubMed

    Gordon, C J; Stead, A G

    1988-04-01

    This study was designed to assess the effects of ethyl alcohol (ethanol) administration on behavioral and autonomic thermoregulation in mice subjected to severe hypothermia or hyperthermia. Male mice of the BALB/c strain were injected intraperitoneally with ethanol at dosages of 0, 0.3, 1.0, or 3.0 g/kg and then placed within a hot environmental chamber to raise their body temperature to 41 degrees C or, alternatively, within a cold chamber to lower it to 28 degrees C. Once the desired hypothermic or hyperthermic state was achieved, the mice were removed from the chamber and placed in either a temperature gradient to monitor behavioral thermoregulatory responses or in an environmental chamber thermostabilized at an ambient temperature (Ta) of 28 degrees C to monitor metabolic rate. The 3.0 g/kg dosage significantly affected behavioral thermoregulatory responses of the hyperthermic mice when initially placed in the temperature gradient. The ability to increase metabolic rate following hypothermia was significantly suppressed at 3.0 g/kg. Dosages of 1.0 and 3.0 g/kg inhibited metabolic rate of hyperthermic mice. Both hypothermic and hyperthermic mice given 3.0 g/kg of ethanol had colonic temperatures significantly below normal after placement in the temperature gradient and metabolic chamber. In conclusion, relatively large dosages of ethanol impair behavioral and autonomic thermoregulation and may lower the set-point for the control of body temperature in mice. PMID:3413196

  15. Effect of body hypothermia on transventricular simple-capacitor-discharge defibrillation thresholds.

    PubMed

    Arredondo, M T; Armayor, M R; Clavin, O E; Valentinuzzi, M E; Scidá, E E

    1980-05-01

    In 260 successful transventricular simple capacitor-discharge defibrillations performed on 20 mongrel dogs under conditions of body hypothermia, an overall average peak current threshold of 69.5 mA/g of heart (SD 30.4) was found. This value, when compared by means of the unpaired t test with previous data obtained under conditions of relative normothermia (89.5 mA/g of heart, SD 32.8, 346 defibrillations, 20 dogs) yielded a highly significant difference (P less than 0.1%). When comparing the deviation of the regression equation (current vs. temperature) from the horizontal line, the Snedecor F test gave also a high level of significance (P less than 1%). These results led to the conclusion that body hypothermia significantly reduces transventricular defibrillation thresholds. After normalizing the regression equations, this reduction was found to be on the average equal to 4.1%/degrees C (SD 1.4) for current and to 5.9%/degrees C (SD 1.4) for energy over the 20 dogs. In all animals, the coefficient of variation was greater for energy than for current (about twice as much), suggesting that current is a better descriptor of what is needed for electrical defibrillation. The transventricular impedance was rather constant, yielding an overall average of 28.5 omega (SD 6.0). PMID:7377363

  16. Nitric oxide in the nucleus raphe magnus modulates cutaneous blood flow in rats during hypothermia

    PubMed Central

    Arami, Masoumeh Kourosh; zade, Javad Mirnajafi; Komaki, Alireza; Amiri, Mahmood; Mehrpooya, Sara; Jahanshahi, Ali; Jamei, Behnam

    2015-01-01

    Objective(s): Nucleus Raphe Magnus (NRM) that is involved in the regulation of body temperature contains nitric oxide (NO) synthase. Considering the effect of NO on skin blood flow control, in this study, we assessed its thermoregulatory role within the raphe magnus. Materials and Methods: To this end, tail blood flow of male Wistar rats was measured by laser doppler following the induction of hypothermia. Results: Intra-NRM injection of SNP (exogenous NO donor, 0.1- 0.2 μl, 0.2 nM) increased the blood flow. Similarly, unilateral microinjection of glutamate (0.1- 0.2 μl, 2.3 nM) into the nucleus increased the blood flow. This effect of L-glutamate was reduced by prior intra NRM administration of NO synthase inhibitor NG-methyl-L-arginine or NG-nitro-L-arginine methyl ester (L-NAME, 0.1 µl, 100 nM). Conclusion: It is concluded that NO modulates the thermoregulatory response of NRM to hypothermia and may interact with excitatory amino acids in central skin blood flow regulation. PMID:26730333

  17. Automated analysis of background EEG and reactivity during therapeutic hypothermia in comatose patients after cardiac arrest.

    PubMed

    Noirhomme, Quentin; Lehembre, Rémy; Lugo, Zulay Del Rosario; Lesenfants, Damien; Luxen, André; Laureys, Steven; Oddo, Mauro; Rossetti, Andrea O

    2014-01-01

    Visual analysis of electroencephalography (EEG) background and reactivity during therapeutic hypothermia provides important outcome information, but is time-consuming and not always consistent between reviewers. Automated EEG analysis may help quantify the brain damage. Forty-six comatose patients in therapeutic hypothermia, after cardiac arrest, were included in the study. EEG background was quantified with burst-suppression ratio (BSR) and approximate entropy, both used to monitor anesthesia. Reactivity was detected through change in the power spectrum of signal before and after stimulation. Automatic results obtained almost perfect agreement (discontinuity) to substantial agreement (background reactivity) with a visual score from EEG-certified neurologists. Burst-suppression ratio was more suited to distinguish continuous EEG background from burst-suppression than approximate entropy in this specific population. Automatic EEG background and reactivity measures were significantly related to good and poor outcome. We conclude that quantitative EEG measurements can provide promising information regarding current state of the patient and clinical outcome, but further work is needed before routine application in a clinical setting. PMID:24452769

  18. Why are Wischnewski spots not always present in lethal hypothermia? The results of testing a stress-reduced animal model.

    PubMed

    Bright, Fiona; Winskog, Calle; Walker, Melissa; Byard, Roger W

    2013-08-01

    Hypothermic fatalities in humans are characterized by a range of often subtle pathological findings that typically include superficial erosive gastritis (Wischnewski spots). Experimental studies have been successfully performed using animal models to replicate this finding, however study animals have inevitably been subjected to a variety of additional stressors including food deprivation, restraint and partial immersion in water while conscious. As it is recognised that stress on its own may cause superficial erosive gastritis, a model has been developed to enable the study of the effects of hypothermia in isolation. 42 Sprague-Dawley rats were allowed free social contact and were fed and watered ad libitum prior to being anaesthetized with isoflurane. Once unconscious, rats were placed on drape cloth covering metal mesh platforms in a styrofoam box packed with ice. The apparatus enabled both maintenance of a specific low temperature (26 °C) in 14 animals, and continued reduction of core temperatures in the remaining 28 (who all died of hypothermia under anaesthesia). Examination of the gastric mucosa in both groups macroscopically and microscopically failed to demonstrate typical Wischnewski spots in any of the 42 animals. Thus, in this model, death from hypothermia occurred without the development of these lesions. These results suggest that stress may be a significant effect modifier in the development of Wischnewski spots in lethal hypothermia. PMID:23910881

  19. Mild hypothermia combined with neural stem cell transplantation for hypoxic-ischemic encephalopathy: neuroprotective effects of combined therapy

    PubMed Central

    Wang, Lin; Jiang, Feng; Li, Qifeng; He, Xiaoguang; Ma, Jie

    2014-01-01

    Neural stem cell transplantation is a useful treatment for ischemic stroke, but apoptosis often occurs in the hypoxic-ischemic environment of the brain after cell transplantation. In this study, we determined if mild hypothermia (27–28°C) can increase the survival rate of neural stem cells (1.0 × 105/μL) transplanted into neonatal mice with hypoxic-ischemic encephalopathy. Long-term effects on neurological functioning of the mice were also examined. After mild hypothermia combined with neural stem cell transplantation, we observed decreased expression levels of inflammatory factor nuclear factor-kappa B and apoptotic factor caspase-3, reduced cerebral infarct volumes, increased survival rate of transplanted cells, and marked improvements in neurological function. Thus, the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation are superior to those of monotherapy. Moreover, our findings suggest that the neuroprotective effects of mild hypothermia combined with neural stem cell transplantation on hypoxic-ischemic encephalopathy are achieved by anti-inflammatory and anti-apoptotic mechanisms. PMID:25422635

  20. A Proposed Methodology to Control Body Temperature in Patients at Risk of Hypothermia by means of Active Rewarming Systems

    PubMed Central

    Costanzo, Silvia; Cusumano, Alessia; Giaconia, Carlo; Mazzacane, Sante

    2014-01-01

    Hypothermia is a common complication in patients undergoing surgery under general anesthesia. It has been noted that, during the first hour of surgery, the patient's internal temperature (Tcore) decreases by 0.5–1.5°C due to the vasodilatory effect of anesthetic gases, which affect the body's thermoregulatory system by inhibiting vasoconstriction. Thus a continuous check on patient temperature must be carried out. The currently most used methods to avoid hypothermia are based on passive systems (such as blankets reducing body heat loss) and on active ones (thermal blankets, electric or hot-water mattresses, forced hot air, warming lamps, etc.). Within a broader research upon the environmental conditions, pollution, heat stress, and hypothermia risk in operating theatres, the authors set up an experimental investigation by using a warming blanket chosen from several types on sale. Their aim was to identify times and ways the human body reacts to the heat flowing from the blanket and the blanket's effect on the average temperature Tskin and, as a consequence, on Tcore temperature of the patient. The here proposed methodology could allow surgeons to fix in advance the thermal power to supply through a warming blanket for reaching, in a prescribed time, the desired body temperature starting from a given state of hypothermia. PMID:25485278

  1. CHOLINESTERASE INHIBITION AND HYPOTHERMIA FOLLOWING EXPOSURE TO BINARY MIXTURES OF ANTICHOLINESTERASE AGENTS: LACK OF EVIDENCE FOR CAUSE-AND-EFFECT

    EPA Science Inventory

    Dose-additivity has been the default assumption in risk assessments of pesticides with a common mechanism of action but it has been suspected that there could be non-additive effects. Inhibition of plasma cholinesterase (ChE) activity and hypothermia were used as benchmarks of e...

  2. Effects of Hypoxic-Ischemic Encephalopathy and Whole-Body Hypothermia on Neonatal Auditory Function: A Pilot Study

    PubMed Central

    Mietzsch, Ulrike; Parikh, Nehal A.; Williams, Amber L.; Shankaran, Seetha; Lasky, Robert E.

    2008-01-01

    We assessed the effects of hypoxic-ischemic encephalopathy (HIE) and whole-body hypothermia therapy on auditory brain stem evoked responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We performed serial assessments of ABRs and DPOAEs in newborns with moderate or severe HIE, randomized to hypothermia (n = 4) or usual care (n = 5). Participants were five boys and four girls with mean gestational age (standard deviation) of 38.9 (1.8) weeks. During the first week of life, peripheral auditory function, as measured by the DPOAEs, was disrupted in all nine subjects. ABRs were delayed but central transmission was intact, suggesting a peripheral rather than a central neural insult. By 3 weeks of age, peripheral auditory function normalized. Hypothermia temporarily prolonged the ABR, more so for waves generated higher in the brain stem but the effects reversed quickly on rewarming. Neonatal audiometric testing is feasible, noninvasive, and capable of enhancing our understanding of the effects of HIE and hypothermia on auditory function. PMID:18720323

  3. Molecular pathology of pulmonary edema in forensic autopsy cases with special regard to fatal hyperthermia and hypothermia.

    PubMed

    Wang, Qi; Ishikawa, Takaki; Michiue, Tomomi; Zhu, Bao-Li; Guan, Da-Wei; Maeda, Hitoshi

    2013-05-10

    Fatalities due to an extreme ambient temperature might present with poor or nonspecific pathologies; thus, the diagnosis of the cause of death in such cases is one of the most difficult tasks in forensic pathology. The present study investigated the molecular pathology of alveolar damage involving pulmonary edema with special regard to hyperthermia (heatstroke) and hypothermia (cold exposure) in forensic autopsy cases (total, n=122; within 48 h postmortem). Intrapulmonary mRNA and immunohistochemical expressions of matrix metalloproteinases (MMPs), intercellular adhesion molecule-1 (ICAM-1), claudin-5 (CLDN-5) and aquaporins (AQPs) were examined. Relative mRNA quantification using Taqman real-time PCR assay demonstrated higher expressions of all markers except for AQP-5 in fatal hyperthermia, and higher expression of MMP-9 in fatal hypothermia. Acute cardiac death, mechanical asphyxiation, fire fatality and intoxication did not present any characteristic findings. In immunostaining, only MMPs showed evident differences among the causes of death: MMP-9 was intensely positive in most cases of hyperthermia and hypothermia, but MMP-2 expression was evident only in hyperthermia. These findings suggest alveolar damage involving pulmonary edema, characteristic of fatal hyperthermia and hypothermia. Systematic analysis of gene expressions using real-time PCR might be a useful procedure in forensic death investigation. PMID:23597750

  4. Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia.

    PubMed

    Lafuente, Hector; Pazos, Maria R; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J; Martinez-Orgado, Jose A

    2016-01-01

    Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult. PMID:27462203

  5. Effects of Cannabidiol and Hypothermia on Short-Term Brain Damage in New-Born Piglets after Acute Hypoxia-Ischemia

    PubMed Central

    Lafuente, Hector; Pazos, Maria R.; Alvarez, Antonia; Mohammed, Nagat; Santos, Martín; Arizti, Maialen; Alvarez, Francisco J.; Martinez-Orgado, Jose A.

    2016-01-01

    Hypothermia is a standard treatment for neonatal encephalopathy, but nearly 50% of treated infants have adverse outcomes. Pharmacological therapies can act through complementary mechanisms with hypothermia improving neuroprotection. Cannabidiol could be a good candidate. Our aim was to test whether immediate treatment with cannabidiol and hypothermia act through complementary brain pathways in hypoxic-ischemic newborn piglets. Hypoxic-ischemic animals were randomly divided into four groups receiving 30 min after the insult: (1) normothermia and vehicle administration; (2) normothermia and cannabidiol administration; (3) hypothermia and vehicle administration; and (4) hypothermia and cannabidiol administration. Six hours after treatment, brains were processed to quantify the number of damaged neurons by Nissl staining. Proton nuclear magnetic resonance spectra were obtained and analyzed for lactate, N-acetyl-aspartate and glutamate. Metabolite ratios were calculated to assess neuronal damage (lactate/N-acetyl-aspartate) and excitotoxicity (glutamate/Nacetyl-aspartate). Western blot studies were performed to quantify protein nitrosylation (oxidative stress), content of caspase-3 (apoptosis) and TNFα (inflammation). Individually, the hypothermia and the cannabidiol treatments reduced the glutamate/Nacetyl-aspartate ratio, as well as TNFα and oxidized protein levels in newborn piglets subjected to hypoxic-ischemic insult. Also, both therapies reduced the number of necrotic neurons and prevented an increase in lactate/N-acetyl-aspartate ratio. The combined effect of hypothermia and cannabidiol on excitotoxicity, inflammation and oxidative stress, and on cell damage, was greater than either hypothermia or cannabidiol alone. The present study demonstrated that cannabidiol and hypothermia act complementarily and show additive effects on the main factors leading to hypoxic-ischemic brain damage if applied shortly after the insult. PMID:27462203

  6. Still cooling after all these years: Meta-analysis of pre-clinical trials of therapeutic hypothermia for acute ischemic stroke.

    PubMed

    Dumitrascu, Oana M; Lamb, Jessica; Lyden, Patrick D

    2016-07-01

    Therapeutic hypothermia is the most potent neuroprotectant for experimental cerebral ischemia, illustrated in a 2007 meta-analysis published in this journal. To address recent therapeutic nihilism, we systematically reviewed recent experimental literature. Quality scoring showed considerable improvement in study design. Using several outcome measures in a variety of models and species, therapeutic hypothermia was protective compared with normothermia, with powerful and statistically significant normalized treatment effect sizes, in 60 papers comprising 216 comparisons. In the past 5 years, preclinical studies of ischemic stroke re-emphasize that therapeutic hypothermia is potently effective, justifying further development in larger human clinical trials. PMID:27089911

  7. Combination of Temperature-Sensitive Stem Cells and Mild Hypothermia: A New Potential Therapy for Severe Traumatic Brain Injury

    PubMed Central

    Tu, Yue; Chen, Chong; Sun, Hong-Tao; Cheng, Shi-Xiang; Liu, Xiao-Zhi; Qu, Yang; Li, Xiao-hong

    2012-01-01

    Abstract Stem cell transplantation holds great potential for the treatment of traumatic brain injury (TBI). However, the micro-environment of reduced oxygen and accumulated toxins leads to low survival rates of grafted cells, which dramatically limits their clinical application. Mild hypothermia has been demonstrated to improve the micro-environment after severe TBI. Thus, we speculate that combinational therapy of mild hypothermia may promote survival of grafted cells, especially temperature-sensitive stem cells, which show the most activity in mild temperatures. In this study, we first isolated mesenchymal stem cells from umbilical cord (UCSMCs) and generated the temperature-sensitive UCSMCs (tsUCSMCs) by infection with a retrovirus carrying the temperature-sensitive tsA58 SV40 LT antigen gene. We demonstrated that tsUCSMCs grew and proliferated with more activity at 33°C than at 37°C by counting cell numbers with a hematocytometer, measuring the cell cycle with flow cytometry, and detecting proliferating cell nuclear antigen (PCNA) with immunofluorescence staining. Thereafter, we established the rat severe TBI model by fluid percussion, and injected PBS, UCSMCs, or tsUCSMCs into the injured region, and subject the animals to normothermia or mild hypothermia (33°C). We found that, compared with UCSMC or tsUCSMC treatment alone, their combination with hypothermia could significantly improve motor and cognitive function with more survival of the grafted cells. Furthermore, we observed that combined therapy with hypothermia and tsUCSMCs exerted the most protective effect on the recovery of neurological function of all the tested treatments, with the highest survival and proliferation rates, and the lowest apoptosis rate. Thus this may represent a new therapeutic strategy for the treatment of severe TBI. PMID:22655683

  8. The effect of therapeutic hypothermia on the expression of inflammatory response genes following moderate traumatic brain injury in the rat.

    PubMed

    Truettner, Jessie S; Suzuki, Takamoto; Dietrich, W Dalton

    2005-08-18

    Traumatic brain injury (TBI) initiates a cascade of cellular and molecular responses including both pro- and anti-inflammatory. Although post-traumatic hypothermia has been shown to improve outcome in various models of brain injury, the underlying mechanisms responsible for these effects have not been clarified. In this study, inflammation cDNA arrays and semi-quantitative RT-PCR were used to detect genes that are differentially regulated after TBI. In addition, the effect of post-traumatic hypothermia on the expression of selective genes was also studied. Rats (n = 6-8 per group) underwent moderate fluid-percussion (F-P) brain injury with and without hypothermic treatment (33 degrees C/3 h). RNA from 3-h or 24-h survival was analyzed for the expression of IL1-beta, IL2, IL6, TGF-beta2, growth-regulated oncogene (GRO), migration inhibitory factor (MIF), and MCP (a transcription factor). The interleukins IL-1beta, IL-2, and IL-6 and TGF-beta and GRO were strongly upregulated early and transiently from 2- to 30-fold over sham at 3 h, with normalization by 24 h. In contrast, the expressions of MIF and MCP were both reduced by TBI compared to sham. Post-traumatic hypothermia had no significant effect on the acute expression of the majority of genes investigated. However, the expression of TGF-beta2 at 24 h was significantly reduced by temperature manipulation. The mechanism by which post-traumatic hypothermia is protective may not involve a general genetic response of the inflammatory genes. However, specific genes, including TGF-beta2, may be altered and effect cell death mechanisms after TBI. Hypothermia differentially regulates certain genes and may target more delayed responses underlying the secondary damage following TBI. PMID:15922484

  9. The influence of body composition on therapeutic hypothermia: a prospective observational study of patients after cardiac arrest

    PubMed Central

    Jimmink, Joost J; Binnekade, Jan M; Paulus, Frederique; Mathus-Vliegen, Elisebeth MH; Schultz, Marcus J; Vroom, Margreeth B

    2008-01-01

    Introduction Patients after out-of-hospital cardiac arrest (OHCA) benefit from therapeutic hypothermia for 24 hours. The time needed to reach hypothermia (target temperature of 32°C to 34°C) varies widely. In this study, we explore the relation between measures of body composition and the time needed to reach target temperature with hypothermia. Method We conducted a prospective observational study in patients treated with hypothermia after OHCA. Data collected included weight and height, body composition by anthropometric measures and by single-frequency body impedance, and waist-to-hip ratio. Analysis of concordance between impedance and anthropometric measures and hazard ratios of achieving target temperature (event) corrected for different body composition measures. Results Twenty-seven patients were included. The median (interquartile range) time to reach target temperature after admission to the intensive care unit was 191 (105 to 382) minutes. Intraclass correlation for total body fat (TBF) measures was 0.94 (95% confidence interval [CI] 0.89 to 0.97). Only TBF percentage (anthropometrics by the Durnin's table) appeared to be associated with time to reach target temperature: 0.93 (95% CI 0.87 to 0.99; P = 0.03). Conclusion The body composition measures from single-frequency impedance and anthropometrics appear to be very concordant. Only TBF percentage (anthropometrics) showed a significant but clinically irrelevant influence on time needed to achieve target temperature with hypothermia. We conclude that there are no indications to adjust current cooling practice toward the body composition of patients. PMID:18616810

  10. Improving neurological outcomes post-cardiac arrest in a rat model: immediate hypothermia and quantitative EEG monitoring

    PubMed Central

    Jia, Xiaofeng; Koenig, Matthew A.; Shin, Hyun-Chool; Zhen, Gehua; Pardo, Carlos A.; Hanley, Daniel F.; Thakor, Nitish V.; Geocadin, Romergryko G.

    2008-01-01

    Summary Objectives Therapeutic hypothermia (TH) after cardiac arrest (CA) improves outcomes in a fraction of patients. To enhance the administration of TH, we studied brain electrophysiological monitoring in determining the benefit of early initiation of TH compared to conventional administration in a rat model. Methods Using an asphyxial CA model, we compared the benefit of immediate hypothermia (IH, T=33°C, immediately post-resuscitation, maintained 6 hours) to conventional hypothermia (CH, T=33°C, starting 1 hour post-resuscitation, maintained 12 hours) via surface cooling. We tracked quantitative EEG using relative entropy (qEEG) with outcome verification by serial Neurological Deficit Score (NDS) and quantitative brain histopathological damage scoring (HDS). Thirty-two rats were divided into 4 groups based on CH/IH and 7/9-minute duration of asphyxial CA. Four sham rats were included for evaluation of the effect of hypothermia on qEEG. Results The 72-hour NDS of the IH group was significantly better than the CH group for both 7-minute (74/63; Median, IH/CH, p<0.001) and 9-minute (54/47, p=0.022) groups. qEEG showed greater recovery with IH (p<0.001) and significantly less neuronal cortical injury by HDS (IH: 18.9±2.5% versus CH: 33.2±4.4%, p=0.006). The 1-hour post-resuscitation qEEG correlated well with 72-hour NDS (p<0.05) and 72-hour behavioral subgroup of NDS (p<0.01). No differences in qEEG were noted in the sham group. Conclusions Immediate but shorter hypothermia compared to CH leads to better functional outcome in rats after 7- and 9- minute CA. The beneficial effect of IH was readily detected by neuro-electrophysiological monitoring and histological changes supported the value of this observation. PMID:17936492

  11. Risk of Hypothermia in a New Olympic Event: the 10-km Marathon Swim

    PubMed Central

    Castro, Renata R. T.; Mendes, Fernanda SNS; Nobrega, Antonio Claudio L.

    2009-01-01

    INTRODUCTION: There are no available data addressing the potential clinical risks of open-water swimming competitions. OBJECTIVE: Address the risks of hypothermia and hypoglycemia during a 10-km open-water swimming competition in order to alert physicians to the potential dangers of this recently-introduced Olympic event. METHODS: This was an observational cross-sectional study, conducted during a 10-km open-water event (water temperature 21°C). The highest ranked elite open-water swimmers in Brazil (7 men, 5 women; ages 21±7 years old) were submitted to anthropometrical measurements on the day before competition. All but one athlete took maltodextrine ad libitum during the competition. Core temperature and capillary glycemia data were obtained before and immediately after the race. RESULTS: Most athletes (83%) finished the race with mild to moderate hypothermia (core temperature <35°C). The body temperature drop was more pronounced in female athletes (4.2±0.7°C vs. male: 2.7±0.8°C; p=0.040). When data from the athlete who did not take maltodextrine was excluded, capillary glycemia increased among athletes (pre 86.6±8.9 mg/dL; post 105.5±26.9 mg/dL; p=0.014). Time to complete the race was inversely related to pre- competition body temperature in men (r=−0.802; p=0.030), while it was inversely correlated with the change in capillary glycemia in women (r=−0.898; p=0.038). CONCLUSION: Hypothermia may occur during open-water swimming events even in elite athletes competing in relatively warm water. Thus, core temperature must be a chief concern of any physician during an open-water swim event. Capillary glycemia may have positive effects on performance. Further studies that include more athletes in a controlled setting are warranted. PMID:19488594

  12. Bullous Lesions After Use of a Commercial Therapeutic Hypothermia Temperature Management System: A Possible Burn Injury?

    PubMed Central

    Wells, James M.; Rizk, Dana V.

    2013-01-01

    Therapeutic hypothermia (TH) is a novel technique for improving the likelihood of survival with good neurologic outcome after cardiopulmonary arrest. While commercial temperature management systems (TMS) are intended to facilitate cooling of the body during TH, their operation also involves body exposure to heat. We describe the case of a 72-year-old female postarrest patient who underwent TH using a commercial water-circulating TMS and concurrent continuous renal replacement therapy. The patient developed bullous lesions on the thigh and torso suspected to constitute a scald burn injury from the TMS. Clinicians must be aware of this important adverse event when providing TH, especially in the setting of concurrent hemodialysis therapy. PMID:24066269

  13. Effect of ultra-fast mild hypothermia using total liquid ventilation on hemodynamics and respiratory mechanics.

    PubMed

    Sage, Michaël; Nadeau, Mathieu; Kohlhauer, Matthias; Praud, Jean-Paul; Tissier, Renaud; Robert, Raymond; Walti, Hervé; Micheau, Philippe

    2016-08-01

    Ultra-fast cooling for mild therapeutic hypothermia (MTH) has several potential applications, including prevention of post-cardiac arrest syndrome. Ultra-fast MTH by total liquid ventilation (TLV) entails the sudden filling of the lungs with a cold perfluorocarbon liquid and its subsequent use to perform TLV. The present physiological study was aimed at assessing whether pulmonary and systemic hemodynamics as well as lung mechanics are significantly altered during this procedure. Pulmonary and systemic arterial pressures, cardiac output as well as airway resistance and respiratory system compliance were measured during ultra-fast MTH by TLV followed by rewarming and normothermia in six healthy juvenile lambs. Results show that none of the studied variables were altered upon varying the perfluorocarbon temperature from 12 to 41 °C. It is concluded that ultra-fast MTH by TLV does not have any deleterious effect on hemodynamics or lung mechanics in healthy juvenile lambs. PMID:27242031

  14. Equilibria Between Cell Membranes and Electrolyte Solution: Effect of Fatal Accidental Hypothermia.

    PubMed

    Petelska, Aneta D; Kotyńska, Joanna; Naumowicz, Monika; Figaszewski, Zbigniew A

    2016-06-01

    Equilibria between the membranes of erythrocytes as well as thrombocytes and solution ions in fatal accidental hypothermia were analyzed using a theoretical four-equilibria model. The model was developed to determinate parameters characterizing cell membrane-surrounding ion interactions: the total surface concentrations of both acidic and basic groups C A, C B, and association constants K AH, K BOH. Knowledge of these parameters was necessary to calculate the theoretical values of surface charge density. The model was validated by curve-fitting the experimental data points to simulated data generated by the model. The experimental and theoretical surface charge density values agree at pH 2-8, at higher pH the deviation was observed. PMID:26843064

  15. G-protein-gated potassium (GIRK) channels containing the GIRK2 subunit are control hubs for pharmacologically induced hypothermic responses.

    PubMed

    Costa, Alberto C S; Stasko, Melissa R; Stoffel, Markus; Scott-McKean, Jonah J

    2005-08-24

    Hypothermic responses of rodents to the peripheral or intraventricular injection of many individual neurotransmitter receptor agonists have been well documented. Because many hypothermia-inducing agonists are also known to activate G-protein-gated potassium (GIRK) channels, we investigated the hypothermic response to several of these agents on Girk2 null mutant mice. Core body temperatures were measured through radiotelemetry, and animals were maintained in special temperature-regulated chambers to ensure the accuracy of the measurements. The resulting data indicate that the activation of GIRK2-containing potassium channels plays a significant role in hypothermia induced by the activation of serotonergic (5-HT(1A)), GABAergic (GABA(B)), muscarinic (m2), adenosine (A1), and mu, delta, and kappa opioid receptors. These channels also are involved in the alcohol-induced hypothermic response. These results have implications for the understanding of pharmacologically induced hypothermia and thermoregulatory mechanisms. PMID:16120781

  16. Right axillary and femoral artery perfusion with mild hypothermia for aortic arch replacement

    PubMed Central

    2014-01-01

    Objectives Aortic arch replacement is associated with increased mortality and morbidity especially in acute type-A aortic dissection. Although hypothermic circulatory arrest with selective antegrade cerebral perfusion has been widely used because of its excellent cerebral protection, its optimal perfusion characteristics are unknown. The present study investigates clinical results obtained after perfusion method modification and temperature management during cardiopulmonary bypass (CPB). Methods Between July 2010 and August 2012, 16 consecutive adult patients (mean age 50.0 yr ± 14.1 yr, range 25 yr to 73 yr, 12 males, 4 females) who presented with acute Stanford type-A aortic dissection underwent aortic arch replacement (total arch, n = 11; hemiarch, n = 5) under mild hypothermia (31.1°C ± 1.5°C) with right axillary and femoral artery perfusion. Results The mean CPB time was 201 min ± 53 min, and the mean myocardial ischemic time was 140 min ± 42 min. The mean selective cerebral perfusion time was 80 min ± 16 min, and the mean lower-body circulatory arrest time was 20 min ± 13 min. No patient death occurred within 30 post-operative days. The following details were observed: new post-operative permanent neurologic deficit in 1 patient (6.3%), temporary neurologic deficit in 2 patients (12.5%), acute renal dysfunction (creatinine level > 230 umol/L) in 3 patients (18.8%) and mechanical ventilation > 72 h in 5 patients (31.2%). Conclusions Aortic arch replacement for acute type-A aortic dissection under mild hypothermia with right axillary and femoral artery perfusion could be safely performed in the patient cohort. PMID:24885031

  17. Temperature Profile and Outcomes of Neonates Undergoing Whole Body Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy

    PubMed Central

    Shankaran, Seetha; Laptook, Abbot R.; McDonald, Scott A.; Higgins, Rosemary D.; Tyson, Jon E.; Ehrenkranz, Richard A.; Das, Abhik; Sant’Anna, Guilherme; Goldberg, Ronald N.; Bara, Rebecca; Walsh, Michele C.

    2011-01-01

    BACKGROUND Decreases below target temperature were noted among neonates undergoing cooling in the NICHD Neonatal Research Network Trial of whole body hypothermia for neonatal hypoxic-ischemic encephalopathy. OBJECTIVE To examine the temperature profile and impact on outcome among ≥ 36 week gestation neonates randomized at ≤ 6 hours of age targeting esophageal temperature of 33.5°C for 72 hours. DESIGN/SETTING/PATIENTS Infants with intermittent temperatures recorded < 32.0°C during induction and maintenance of cooling were compared to all other cooled infants and relationship with outcome at 18 months was evaluated. RESULTS There were no differences in stage of encephalopathy, acidosis, or 10 minute Apgar scores between infants with temperatures < 32.0°C during induction (n=33) or maintenance (n=10) and all other infants who were cooled (n=58); however birth weight was lower and need for blood pressure support higher among infants with temperatures < 32.0 °C compared to all other cooled infants. No increase in acute adverse events were noted among infants with temperatures < 32.0 °C and hours spent < 32°C were not associated with the primary outcome of death or moderate/severe disability or the Bayley II Mental Developmental Index at 18 months. CONCLUSION Term infants with a lower birth weight are at risk for decreasing temperatures < 32.0°C while undergoing body cooling using a servo controlled system. This information suggests extra caution during the application of hypothermia as these lower birth weight infants are at risk for overcooling. Our findings may assist in planning additional trials of lower target temperature for neonatal hypoxic-ischemic encephalopathy. PMID:21499182

  18. MRI Detection of Brown Adipose Tissue with Low Fat Content in Newborns with Hypothermia

    PubMed Central

    Hu, Houchun H.; Wu, Tai-Wei; Yin, Larry; Kim, Mimi S.; Chia, Jonathan M.; Perkins, Thomas G.; Gilsanz, Vicente

    2013-01-01

    Purpose To report the observation of brown adipose tissue (BAT) with low fat content in neonates with hypoxic-ischemic encephalopathy (HIE) after they have undergone hypothermia therapy. Materials and Methods The local ethics committee approved the imaging study. Ten HIE neonates (3 males, 7 females, age range: 2-3 days) were studied on a 3T MRI system using a low-flip-angle (3 degrees) six-echo proton-density-weighted chemical-shift-encoded water-fat pulse sequence. Fat-signal fraction (FF) measurements of supraclavicular and interscapular (nape) BAT and adjacent subcutaneous white adipose tissues (WAT) were compared to those from five non-HIE neonates, two recruited for the present investigation and three from a previous study. Results In HIE neonates, the FF range for the supraclavicular, interscapular, and subcutaneous regions were 10.3-29.9%, 28.0-57.9%, and 62.6-88.0%, respectively. In non-HIE neonates, the values were 23.7-42.2% (p=0.01), 45.4-59.5% (p=0.06), and 67.8-86.3% (p=0.38), respectively. On an individual basis, supraclavicular BAT FF was consistently the lowest, interscapular BAT values were higher, and subcutaneous WAT values were the highest (p<0.01). Conclusion We speculate that hypothermia therapy in HIE neonates likely promotes BAT-mediated non-shivering thermogenesis, which subsequently leads to a depletion of the tissue's intracellular fat stores. We believe this is consequently reflected in lower FF values, particularly in the supraclavicular BAT depot, in contrast to non-HIE neonates. PMID:24239336

  19. Xenon Combined with Therapeutic Hypothermia Is Not Neuroprotective after Severe Hypoxia-Ischemia in Neonatal Rats

    PubMed Central

    Sabir, Hemmen; Osredkar, Damjan; Maes, Elke; Wood, Thomas; Thoresen, Marianne

    2016-01-01

    Background Therapeutic hypothermia (TH) is standard treatment following perinatal asphyxia in newborn infants. Experimentally, TH is neuroprotective after moderate hypoxia-ischemia (HI) in seven-day-old (P7) rats. However, TH is not neuroprotective after severe HI. After a moderate HI insult in newborn brain injury models, the anesthetic gas xenon (Xe) doubles TH neuroprotection. The aim of this study was to examine whether combining Xe and TH is neuroprotective as applied in a P7 rat model of severe HI. Design/Methods 120 P7 rat pups underwent a severe HI insult; unilateral carotid artery ligation followed by hypoxia (8% O2 for 150min at experimental normothermia (NT-37: Trectal 37°C). Surviving pups were randomised to immediate NT-37 for 5h (n = 36), immediate TH-32: Trectal 32°C for 5h (n = 25) or immediate TH-32 plus 50% inhaled Xe for 5h (n = 24). Pups were sacrificed after one week of survival. Relative area loss of the ligated hemisphere was measured, and neurons in the subventricular zone of this injured hemisphere were counted, to quantify brain damage. Results Following the HI insult, median (interquartile range, IQR) hemispheric brain area loss was similar in all groups: 63.5% (55.5–75.0) for NT-37 group, 65.0% (57.0–65.0) for TH-32 group, and 66.5% (59.0–72.0) for TH-32+Xe50% group (not significant). Correspondingly, there was no difference in neuronal cell count (NeuN marker) in the subventricular zone across the three treatment groups. Conclusions Immediate therapeutic hypothermia with or without additional 50% inhaled Xe, does not provide neuroprotection one week after severe HI brain injury in the P7 neonatal rat. This model aims to mimic the clinical situation in severely asphyxiated neonates and treatment these newborns remains an ongoing challenge. PMID:27253085

  20. Cost-effective therapeutic hypothermia treatment device for hypoxic ischemic encephalopathy.

    PubMed

    Kim, John J; Buchbinder, Nathan; Ammanuel, Simon; Kim, Robert; Moore, Erika; O'Donnell, Neil; Lee, Jennifer K; Kulikowicz, Ewa; Acharya, Soumyadipta; Allen, Robert H; Lee, Ryan W; Johnston, Michael V

    2013-01-01

    Despite recent advances in neonatal care and monitoring, asphyxia globally accounts for 23% of the 4 million annual deaths of newborns, and leads to hypoxic-ischemic encephalopathy (HIE). Occurring in five of 1000 live-born infants globally and even more in developing countries, HIE is a serious problem that causes death in 25%-50% of affected neonates and neurological disability to at least 25% of survivors. In order to prevent the damage caused by HIE, our invention provides an effective whole-body cooling of the neonates by utilizing evaporation and an endothermic reaction. Our device is composed of basic electronics, clay pots, sand, and urea-based instant cold pack powder. A larger clay pot, lined with nearly 5 cm of sand, contains a smaller pot, where the neonate will be placed for therapeutic treatment. When the sand is mixed with instant cold pack urea powder and wetted with water, the device can extract heat from inside to outside and maintain the inner pot at 17°C for more than 24 hours with monitoring by LED lights and thermistors. Using a piglet model, we confirmed that our device fits the specific parameters of therapeutic hypothermia, lowering the body temperature to 33.5°C with a 1°C margin of error. After the therapeutic hypothermia treatment, warming is regulated by adjusting the amount of water added and the location of baby inside the device. Our invention uniquely limits the amount of electricity required to power and operate the device compared with current expensive and high-tech devices available in the United States. Our device costs a maximum of 40 dollars and is simple enough to be used in neonatal intensive care units in developing countries. PMID:23319871

  1. Outcome-related metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of oxygen–glucose deprivation in a neonatal brain slice model of asphyxia

    PubMed Central

    Liu, Jia; Litt, Lawrence; Segal, Mark R; Kelly, Mark J S; Yoshihara, Hikari A I; James, Thomas L

    2011-01-01

    Human clinical trials using 72 hours of mild hypothermia (32°C–34°C) after neonatal asphyxia have found substantially improved neurologic outcomes. As temperature changes differently modulate numerous metabolite fluxes and concentrations, we hypothesized that 1H/31P nuclear magnetic resonance (NMR) spectroscopy of intracellular metabolites can distinguish different insults, treatments, and recovery stages. Three groups of superfused neonatal rat brain slices underwent 45 minutes oxygen–glucose deprivation (OGD) and then were: treated for 3 hours with mild hypothermia (32°C) that began with OGD, or similarly treated with hypothermia after a 15-minute delay, or not treated (normothermic control group, 37°C). Hypothermia was followed by 3 hours of normothermic recovery. Slices collected at different predetermined times were processed, respectively, for 14.1 Tesla NMR analysis, enzyme-linked immunosorbent assay (ELISA) cell-death quantification, and superoxide production. Forty-nine NMR-observable metabolites underwent a multivariate analysis. Separated clustering in scores plots was found for treatment and outcome groups. Final ATP (adenosine triphosphate) levels, severely decreased at normothermia, were restored equally by immediate and delayed hypothermia. Cell death was decreased by immediate hypothermia, but was equally substantially greater with normothermia and delayed hypothermia. Potentially important biomarkers in the 1H spectra included PCr-1H (phosphocreatine in the 1H spectrum), ATP-1H (adenosine triphosphate in the 1H spectrum), and ADP-1H (adenosine diphosphate in the 1H spectrum). The findings suggest a potential role for metabolomic monitoring during therapeutic hypothermia. PMID:20717124

  2. Outcome-related metabolomic patterns from 1H/31P NMR after mild hypothermia treatments of oxygen-glucose deprivation in a neonatal brain slice model of asphyxia.

    PubMed

    Liu, Jia; Litt, Lawrence; Segal, Mark R; Kelly, Mark J S; Yoshihara, Hikari A I; James, Thomas L

    2011-02-01

    Human clinical trials using 72 hours of mild hypothermia (32°C-34°C) after neonatal asphyxia have found substantially improved neurologic outcomes. As temperature changes differently modulate numerous metabolite fluxes and concentrations, we hypothesized that (1)H/(31)P nuclear magnetic resonance (NMR) spectroscopy of intracellular metabolites can distinguish different insults, treatments, and recovery stages. Three groups of superfused neonatal rat brain slices underwent 45 minutes oxygen-glucose deprivation (OGD) and then were: treated for 3 hours with mild hypothermia (32°C) that began with OGD, or similarly treated with hypothermia after a 15-minute delay, or not treated (normothermic control group, 37°C). Hypothermia was followed by 3 hours of normothermic recovery. Slices collected at different predetermined times were processed, respectively, for 14.1 Tesla NMR analysis, enzyme-linked immunosorbent assay (ELISA) cell-death quantification, and superoxide production. Forty-nine NMR-observable metabolites underwent a multivariate analysis. Separated clustering in scores plots was found for treatment and outcome groups. Final ATP (adenosine triphosphate) levels, severely decreased at normothermia, were restored equally by immediate and delayed hypothermia. Cell death was decreased by immediate hypothermia, but was equally substantially greater with normothermia and delayed hypothermia. Potentially important biomarkers in the (1)H spectra included PCr-(1)H (phosphocreatine in the (1)H spectrum), ATP-(1)H (adenosine triphosphate in the (1)H spectrum), and ADP-(1)H (adenosine diphosphate in the (1)H spectrum). The findings suggest a potential role for metabolomic monitoring during therapeutic hypothermia. PMID:20717124

  3. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

    PubMed Central

    2012-01-01

    Background Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2–3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. Methods/Design Term newborns (gestational age ≥ 36 weeks and birth weight ≥ 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial

  4. Mild hypothermia combined with a scaffold of NgR-silenced neural stem cells/Schwann cells to treat spinal cord injury

    PubMed Central

    Wang, Dong; Liang, Jinhua; Zhang, Jianjun; Liu, Shuhong; Sun, Wenwen

    2014-01-01

    Because the inhibition of Nogo proteins can promote neurite growth and nerve cell differentiation, a cell-scaffold complex seeded with Nogo receptor (NgR)-silenced neural stem cells and Schwann cells may be able to improve the microenvironment for spinal cord injury repair. Previous studies have found that mild hypothermia helps to attenuate secondary damage in the spinal cord and exerts a neuroprotective effect. Here, we constructed a cell-scaffold complex consisting of a poly(D,L-lactide-co-glycolic acid) (PLGA) scaffold seeded with NgR-silenced neural stem cells and Schwann cells, and determined the effects of mild hypothermia combined with the cell-scaffold complexes on the spinal cord hemi-transection injury in the T9 segment in rats. Compared with the PLGA group and the NgR-silencing cells + PLGA group, hindlimb motor function and nerve electrophysiological function were clearly improved, pathological changes in the injured spinal cord were attenuated, and the number of surviving cells and nerve fibers were increased in the group treated with the NgR-silenced cell scaffold + mild hypothermia at 34°C for 6 hours. Furthermore, fewer pathological changes to the injured spinal cord and more surviving cells and nerve fibers were found after mild hypothermia therapy than in injuries not treated with mild hypothermia. These experimental results indicate that mild hypothermia combined with NgR gene-silenced cells in a PLGA scaffold may be an effective therapy for treating spinal cord injury. PMID:25657741

  5. [The first application of therapeutic hypothermia in Poland--selective head cooling (Cool-Cap) with whole-body moderate hypothermia in a newborn with features of hypoxic ischemic encephalopathy].

    PubMed

    Gulczyńska, Ewa; Kesiak, Marcin; Kryszczyńska, Joanna; Gadzinowski, Janusz; Oszukowski, Przemysław

    2012-05-01

    The authors present the first application of therapeutic hypothermia in a newborn in Poland. The female newborn, born with severe asphyxia, was transported to a referral perinatal center where the method of brain cooling was possible. Severe hypoxic ischemic encephalopathy was confirmed by an integrated EEG. During the cooling procedure (which lasted 72 hours), no important side effects were noticed. The neurodevelopmental outcome of the baby assessed during the first 2 years of her life is normal. PMID:22708339

  6. [Regulation of superoxide dismutase activity during deep hypothermia by simultaneous administration of water and lipid soluble antioxidants].

    PubMed

    Shkesters, A P; Utno, L Ia; Girgensone, M Ia

    1991-06-01

    Alongside anti-hypoxia activity, the method of deep hypothermia causes discoordination of metabolism in the heart. This is due to increased secretion of catecholamines in the process of cooling, to activation in free radical generation and lipid peroxidation. Pantethine and alpha-tocopherol were used. Pantethine reduced lipid peroxidation, preserved reaction activity of catalyzing resyntheses and transport of high energetic compounds in the heart, while alpha-tocopherol prevented lipid peroxidation activation and decrease in SOD. Simultaneous use of pantethine and alpha-tocopherol caused increase in SOD and normalization of heart metabolism. Thus, for protection of the heart against excessive free radical generation under deep hypothermia simultaneous use of antioxidants like pantethine and alpha-tocopherol is necessary. PMID:1893178

  7. Recombinant Factor VIIa Reduces Bleeding after Blunt Liver Injury in a Pig Model of Dilutional Coagulopathy under Severe Hypothermia

    PubMed Central

    Spronk, Henri M. H.; Braunschweig, Till; Rossaint, Rolf; Wüst, Dirk C.; van Oerle, Rene; Lauritzen, Brian; Tolba, Rene; Grottke, Oliver

    2015-01-01

    Background Recombinant factor VIIa (rFVIIa) is registered for use in haemophilia with inhibitors and other rare bleeding disorders, but has also been used in various other clinical conditions to terminate life-threatening bleeding. Underlying conditions (e.g. coagulopathy) and dosing may affect treatment efficacy. The objective of the present study was to evaluate the impact of increasing doses of rFVIIa on blood loss and coagulation assays in haemodiluted and hypothermic pigs undergoing blunt liver injury. Methods A grade III blunt liver injury was induced in 28 pigs after 70% haemodilution and cooling to 32.6–33.4°C. Ten minutes after trauma, animals randomly received placebo or 90, 180 or 360 μg/kg rFVIIa. Global coagulation parameters, thromboelastometry (TEM) and plasma thrombin generation (TG) were determined at different time points during the observation period of 120 minutes. Results Total blood loss was significantly lower following 90 μg/kg rFVIIa (1206 [1138–1470] mL) relative to placebo (2677 [2337–3068] mL; p<0.05), with no increased effect with higher dose levels of rFVIIa. Following trauma and haemodilution, coagulation was impaired relative to baseline in both TEM and TG analysis. At 60 and 120 minutes after trauma, TEM variables improved in the rFVIIa-treated animals compared with the placebo group. Similarly, rFVIIa improved coagulation kinetics in TG. As was observed with blood loss, no significant effect between different rFVIIa dose levels was found in TEM or TG. Macro- and microscopic post-mortem examination did not reveal any signs of thromboembolic events. Conclusion Early administration of 90 μg/kg rFVIIa reduced blood loss in pigs undergoing blunt liver injury even after severe haemodilution and hypothermia, with no further effect of higher dose levels. Coagulation assays showed impaired coagulation in coagulopathic animals, with a dose-independent improvement in animals treated with rFVIIa. PMID:26098426

  8. Evidence for the Therapeutic Efficacy of Either Mild Hypothermia or Oxygen Radical Scavengers after Repetitive Mild Traumatic Brain Injury

    PubMed Central

    Miyauchi, Takashi; Wei, Enoch P.

    2014-01-01

    Abstract Repetitive brain injury, particularly that occurring with sporting-related injuries, has recently garnered increased attention in both the clinical and public settings. In the laboratory, we have demonstrated the adverse axonal and vascular consequences of repetitive brain injury and have demonstrated that moderate hypothermia and/or FK506 exerted protective effects after repetitive mild traumatic brain injury (mTBI) when administered within a specific time frame, suggesting a range of therapeutic modalities to prevent a dramatic exacerbation. In this communication, we revisit the utility of targeted therapeutic intervention to seek the minimal level of hypothermia needed to achieve protection while probing the role of oxygen radicals and their therapeutic targeting. Male Sprague-Dawley rats were subjected to repetitive mTBI by impact acceleration injury. Mild hypothermia (35°C, group 2), superoxide dismutase (group 3), and Tempol (group 4) were employed as therapeutic interventions administered 1 h after the repetitive mTBI. To assess vascular function, cerebral vascular reactivity to acetylcholine was evaluated 3 and 4 h after the repetitive mTBI, whereas to detect the burden of axonal damage, amyloid precursor protein (APP) density in the medullospinal junction was measured. Whereas complete impairment of vascular reactivity was observed in group 1 (without intervention), significant preservation of vascular reactivity was found in the other groups. Similarly, whereas remarkable increase in the APP-positive axon was observed in group 1, there were no significant increases in the other groups. Collectively, these findings indicate that even mild hypothermia or the blunting free radical damage, even when performed in a delayed period, is protective in repetitive mTBI. PMID:24341607

  9. Successful use of therapeutic hypothermia after cardiac arrest due to amitriptyline and venlafaxine intoxication.

    PubMed

    Kontio, Terhi; Salo, Ari; Kantola, Teemu; Toivonen, Lauri; Skrifvars, Markus B

    2015-06-01

    The prognosis of out-of-hospital cardiac arrest (OHCA) due to intoxication is dismal. Tricyclic antidepressants (TCAs) are widely used in the treatment of depression, but possess significant cardiotoxicity, and are one of the most common medications used in suicide attempts worldwide. TCA poisoning can cause hypotension, seizures, and cardiac conduction disturbances, which can lead to life-threatening arrhythmia. Current guidelines recommend mild therapeutic hypothermia (TH) for unconscious survivors of OHCA, but hypothermia treatment itself can cause disturbances in cardiac conduction, which could aggravate the effect of TCAs on cardiac conduction. We report the successful use of TH in a 19-year-old woman who was resuscitated from ventricular tachycardia after intentional ingestion of amitriptyline and venlafaxine, a serotonin-norepinephrine reuptake inhibitor. The cardiac arrest was witnessed, but no bystander cardiopulmonary resuscitation (CPR) was performed. The initial rhythm was ventricular tachycardia with no detectable pulse. Three defibrillations, magnesium sulfate, and sodium bicarbonate were given and her trachea was intubated, after which return of spontaneous circulation (ROSC) was achieved in 26 minutes. After ROSC, she had seizures and was sedated with propofol. Out-of-hospital TH was initiated with 1500 mL of cold Ringer's acetate. An infusion of norepinephrine was initiated for low blood pressure. On arrival at the university hospital, she was unconscious and had dilated pupils. She was tachycardic with a body temperature of 33.5°C. She was transferred to the intensive care unit and TH was maintained with invasive cooling. During the TH treatment, she did not experience any serious cardiac arrhythmia, transthoracic echocardiogram was normal, and the electrocardiogram (ECG) returned to normal. The patient was extubated 45 hours after the cardiac arrest. After the extubation, she was alert and cooperative, but slightly delusional. She was

  10. Therapeutic hypothermia in acute liver failure: a multi-center retrospective cohort analysis

    PubMed Central

    Karvellas, Constantine J.; Stravitz, R. Todd; Battenhouse, Holly; Lee, William M.; Schilsky, Michael L.

    2016-01-01

    Background The benefit of therapeutic hypothermia (TH) in Acute Liver Failure (ALF) has not been previously demonstrated in a controlled fashion. This study aimed to determine the impact of TH on 21-day survival and complications in ALF patients at high risk for cerebral edema. Methods Retrospective cohort study of ALF patients in the US ALFSG with Grade III or IV hepatic encephalopathy. TH (32°C – 35°C) was used in 97 (8%) patients; 1135 (92%) not cooled were controls. Results Intracranial pressure (ICP) was monitored in 38 (40%) TH ALF patients (vs. 22% controls, p=0.0001). Rates of bleeding (12% in both), bloodstream (17% vs. 18) and tracheal infections (21% vs. 23%, p> 0.5 for all) were similar. Unadjusted 21-day overall (62% vs. 60%) and transplant-free survival (45 vs. 39%, p>0.4 for both) were similar. Multivariable models were created for acetaminophen (APAP) (n= 582) and non-APAP (n=613) patients. For APAP patients, MELD (Odds ratio 0.91 per increment; 95% CI 0.89–0.94, p <0.001) and vasopressors (OR 0.16; 0.11–0.24, p < 0.0001) were associated with decreased 21-day spontaneous survival. Survival was improved with TH in APAP patients aged < 25y (Age 25: OR 2.735; 95% CI 1.001 – 7.467) but worsened in 64y or older APAP patients (Age = 64: OR 0.167; 95%CI 0.028 – 0.999). For non-APAP patients, MELD (OR 0.93 per increment; 0.91–0.95, p < 0.0001) and vasopressors (OR 0.60; 0.40–0.90, p=0.01) were associated with worse outcomes while TH had no impact (p= 0.93). Conclusions Therapeutic hypothermia in ALF was not associated with increased bleeding or infections. While young APAP-ALF patients may benefit, TH did not consistently impact 21-day survival. A prospective trial is required to clarify the utility of TH in ALF patients. PMID:25308108

  11. Wrist Hypothermia Related to Continuous Work with a Computer Mouse: A Digital Infrared Imaging Pilot Study.

    PubMed

    Reste, Jelena; Zvagule, Tija; Kurjane, Natalja; Martinsone, Zanna; Martinsone, Inese; Seile, Anita; Vanadzins, Ivars

    2015-08-01

    Computer work is characterized by sedentary static workload with low-intensity energy metabolism. The aim of our study was to evaluate the dynamics of skin surface temperature in the hand during prolonged computer mouse work under different ergonomic setups. Digital infrared imaging of the right forearm and wrist was performed during three hours of continuous computer work (measured at the start and every 15 minutes thereafter) in a laboratory with controlled ambient conditions. Four people participated in the study. Three different ergonomic computer mouse setups were tested on three different days (horizontal computer mouse without mouse pad; horizontal computer mouse with mouse pad and padded wrist support; vertical computer mouse without mouse pad). The study revealed a significantly strong negative correlation between the temperature of the dorsal surface of the wrist and time spent working with a computer mouse. Hand skin temperature decreased markedly after one hour of continuous computer mouse work. Vertical computer mouse work preserved more stable and higher temperatures of the wrist (>30 °C), while continuous use of a horizontal mouse for more than two hours caused an extremely low temperature (<28 °C) in distal parts of the hand. The preliminary observational findings indicate the significant effect of the duration and ergonomics of computer mouse work on the development of hand hypothermia. PMID:26262633

  12. Cold Tolerance and Sex-Dependent Hypothermia May Explain Winter Sexual Segregation in a Farmland Bird.

    PubMed

    Powolny, Thibaut; Bretagnolle, Vincent; Dupoué, Andréaz; Lourdais, Olivier; Eraud, Cyril

    2016-01-01

    Migration is an important event in the life cycle of many organisms, but considerable intraspecific variation may occur in its timing and/or destination, resulting in sexual segregation during wintering periods. In this study, we tested the body size hypothesis, or cold tolerance hypothesis, which predicts that body size dimorphism modulates metabolic costs associated with cold climate. Using the Eurasian skylark, we first investigated whether this species showed sexual differential migration. Then we explored the body size hypothesis by experimentally testing the effect of low ambient temperature (Ta) on both metabolic rate (MR) and body temperature (Tb). We tested for sex-related differences in metabolism and in energy-saving mechanism (hypothermia). We found clear differential migration by sex in skylark wintering populations, with a male-biased sex ratio decreasing toward southern latitudes. Measurements on captive birds at 20°, 6°, and -5°C demonstrated a significant increase in MR when Ta decreased, but there is no difference between sexes. While both males and females reduced their Tb overnight, Tb reduction was more pronounced in females exposed to the coldest temperature treatment. In addition, we found that individuals with the most reduced Tb lost less body weight during the night, suggesting that Tb reduction may help minimize energy expenditure when conditions become constraining. Our study suggests that functional mechanisms may be involved in latitudinal segregation between sexes and supports the hypothesis that sex-specific physiological strategies and thermal tolerance may explain segregation between sexes. PMID:27082725

  13. Preventing inadvertent hypothermia: comparing two protocols for preoperative forced-air warming.

    PubMed

    Cobbe, Kerry-Anne; Di Staso, Renatta; Duff, Jed; Walker, Kim; Draper, Nicole

    2012-02-01

    Preoperative forced-air warming is one way of preventing inadvertent perioperative hypothermia. There is scant evidence, however, on the best warming method or the acceptability of these methods to patients. This pilot study compared two warming protocols: one that commenced at maximum temperature and was titrated down as requested (A) and one that commenced at near body temperature and was titrated up as tolerated (B). A crossover design was used in which each participant (n=10) received both protocols sequentially. The mean device temperature and length of time spent at maximum settings were greater for protocol A (43°C±0°C vs 41°C±1°C, P=.003; and 60±0 vs 41.5±2.8 minutes, P=.004). There was no difference in thermal comfort scores, participant temperature, or sweating between the two protocols. When asked, participants preferred protocol A to B (70% to 30%). Starting at higher device settings appears the more favorable of the two approaches. PMID:22264617

  14. [Heterotrophic Nitrification and Aerobic Denitrification of the Hypothermia Aerobic Denitrification Bacterium: Arthrobacter arilaitensis].

    PubMed

    He, Teng-xia; Ni, Jiu-pai; Li, Zhen-lun; Sun, Quan; Ye Qing; Xu, Yi

    2016-03-15

    High concentrations of ammonium, nitrate and nitrite nitrogen were employed to clarify the abilities of heterotrophic nitrification and aerobic denitrification of Arthrobacter arilaitensis strain Y-10. Meanwhile, by means of inoculating the strain suspension into the mixed ammonium and nitrate, ammonium and nitrite nitrogen simulated wastewater, we studied the simultaneous nitrification and denitrification ability of Arthrobacter arilaitensis strain Y-10. In addition, cell optical density was assayed in each nitrogen removal process to analyze the relationship of cell growth and nitrogen removal efficiency. The results showed that the hypothermia denitrification strain Arthrobacter arilaitensis Y-10 exhibited high nitrogen removal efficiency during heterotrophic nitrification and aerobic denitrification. The ammonium, nitrate and nitrite removal rates were 65.0%, 100% and 61.2% respectively when strain Y-10 was cultivated for 4 d at 15°C with initial ammonium, nitrate and nitrite nitrogen concentrations of 208.43 mg · L⁻¹, 201.16 mg · L⁻¹ and 194.33 mg · L⁻¹ and initial pH of 7.2. Nitrite nitrogen could only be accumulated in the medium containing nitrate nitrogen during heterotrophic nitrification and aerobic denitrification process. Additionally, the ammonium nitrogen was mainly removed in the inorganic nitrogen mixed synthetic wastewater. In short, Arthrobacter arilaitensis Y-10 could conduct nitrification and denitrification effectively under aerobic condition and the ammonium nitrogen removal rate was more than 80.0% in the inorganic nitrogen mixed synthetic wastewater. PMID:27337904

  15. Establishing a hypothermia service for infants with suspected hypoxic-ischemic encephalopathy.

    PubMed

    Saliba, Elie; Fakhri, Nadine; Debillon, Thierry

    2015-04-01

    The translation of new treatments based upon established evidence into clinical practice is often difficult. The establishment of a therapeutic hypothermia (TH) service and a related cooling register would provide the opportunity to examine how a new therapy becomes implemented in a country or region. The objectives of a TH program should be: to provide guidance to clinicians who are considering the introduction of this new therapy; to ensure standardized clinical practices; to audit the implementation and conduct of TH; to provide surveillance for cooling-related adverse effects; and to evaluate the subsequent neurodevelopmental outcome. Prior to the use of TH, the most important practices to prioritize during its implementation should be identified and include the following: ensure timely identification of infants with neonatal encephalopathy; develop a coordinated system with the local or regional referral cooling center; develop a transport team capable of performing cooling during transport; ensure that each participating unit has access to a national encephalopathy register, and have developmental follow-up arrangements in place that are appropriate and uniform for the region/country. PMID:25683599

  16. Cerebral oxygen metabolism in neonatal hypoxic ischemic encephalopathy during and after therapeutic hypothermia

    PubMed Central

    Dehaes, Mathieu; Aggarwal, Alpna; Lin, Pei-Yi; Rosa Fortuno, C; Fenoglio, Angela; Roche-Labarbe, Nadège; Soul, Janet S; Franceschini, Maria Angela; Grant, P Ellen

    2014-01-01

    Pathophysiologic mechanisms involved in neonatal hypoxic ischemic encephalopathy (HIE) are associated with complex changes of blood flow and metabolism. Therapeutic hypothermia (TH) is effective in reducing the extent of brain injury, but it remains uncertain how TH affects cerebral blood flow (CBF) and metabolism. Ten neonates undergoing TH for HIE and seventeen healthy controls were recruited from the NICU and the well baby nursery, respectively. A combination of frequency domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) systems was used to non-invasively measure cerebral hemodynamic and metabolic variables at the bedside. Results showed that cerebral oxygen metabolism (CMRO2i) and CBF indices (CBFi) in neonates with HIE during TH were significantly lower than post-TH and age-matched control values. Also, cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) were significantly higher in neonates with HIE during TH compared with age-matched control neonates. Post-TH CBV was significantly decreased compared with values during TH whereas SO2 remained unchanged after the therapy. Thus, FDNIRS–DCS can provide information complimentary to SO2 and can assess individual cerebral metabolic responses to TH. Combined FDNIRS–DCS parameters improve the understanding of the underlying physiology and have the potential to serve as bedside biomarkers of treatment response and optimization. PMID:24064492

  17. A Survey of Accidental Hypothermia Knowledge among Navy Members in China and the Implications for Training

    PubMed Central

    Li, Shuang; Qiu, Chen; Shi, Wenwen; Huang, Yan; Gui, Li

    2016-01-01

    Objectives: Accidental hypothermia (AH) is a potentially life-threatening condition that can lead to significant morbidity and life-long effects. Navy personnel are always at a greater risk of AH due to frequent outdoor work, wilderness exposure, prolonged immobility and exhaustion. The purpose of the survey was to assess Chinese Navy members’ awareness of AH and to make recommendations with regard to better measures for improving it. Methods: 111 Navy members completed a written questionnaire that was subsequently analyzed. Results: 30.6% of the respondents have experienced AH and 64.9% rated their knowledge of AH as “low” or “none”. Over half of them identified the initial symptom of AH as obvious shivering (69.4%) and apathy (45.0%). As for the aggravate symptoms, 60.9% chose the wrong answer of more obvious shivering instead of the right one—absence of shivering (5.4%). In the case of the treatment of mild AH, more than half of the respondents chose the wrong answers. Conclusions: This study suggests that the basic skills of recognition and treatment of AH are inadequate in the Chinese Navy. Further work is required to develop a systematical, comprehensive and corresponding education method that would promote correct actions during AH. PMID:26978382

  18. Hypothermia mediates age-dependent increase of tau phosphorylation in db/db mice.

    PubMed

    El Khoury, Noura B; Gratuze, Maud; Petry, Franck; Papon, Marie-Amélie; Julien, Carl; Marcouiller, François; Morin, Françoise; Nicholls, Samantha B; Calon, Frédéric; Hébert, Sébastien S; Marette, André; Planel, Emmanuel

    2016-04-01

    Accumulating evidence from epidemiological studies suggest that type 2 diabetes is linked to an increased risk of Alzheimer's disease (AD). However, the consequences of type 2 diabetes on AD pathologies, such as tau hyperphosphorylation, are not well understood. Here, we evaluated the impact of type 2 diabetes on tau phosphorylation in db/db diabetic mice aged 4 and 26weeks. We found increased tau phosphorylation at the CP13 epitope correlating with a deregulation of c-Jun. N-terminal kinase (JNK) and Protein Phosphatase 2A (PP2A) in 4-week-old db/db mice. 26-week-old db/db mice displayed tau hyperphosphorylation at multiple epitopes (CP13, AT8, PHF-1), but no obvious change in kinases or phosphatases, no cleavage of tau, and no deregulation of central insulin signaling pathways. In contrast to younger animals, 26-week-old db/db mice were hypothermic and restoration of normothermia rescued phosphorylation at most epitopes. Our results suggest that, at early stages of type 2 diabetes, changes in tau phosphorylation may be due to deregulation of JNK and PP2A, while at later stages hyperphosphorylation is mostly a consequence of hypothermia. These results provide a novel link between diabetes and tau pathology, and underlie the importance of recording body temperature to better understand the relationship between diabetes and AD. PMID:26777665

  19. Intra-operative correction of acidosis, coagulopathy and hypothermia in combat casualties with severe haemorrhagic shock.

    PubMed

    Morrison, J J; Ross, J D; Poon, H; Midwinter, M J; Jansen, J O

    2013-08-01

    We assessed acidosis, coagulopathy and hypothermia, before and after surgery in 51 combat troops operated on for severe blast injury. Patients were transfused a median (IQR [range]) of 27 (17-38 [5-84]) units of red cell concentrate, 27 (16-38 [4-83]) units of plasma, 2.0 (0.5-3.5 [0-13.0]) units of cryoprecipitate and 4 (2-6 [0-17]) pools of platelets. The pH, base excess, prothrombin time and temperature increased: from 7.19 (7.10-7.29 [6.50-7.49]) to 7.45 (7.40-7.51 [7.15-7.62]); from -9.0 (-13.5 to -4.5 [-28 to -2]) mmol.l⁻¹ to 4.5 (1.0-8.0 [-7 to +11]) mmol.l⁻¹; from 18 (15-21 [9-24]) s to 14 (11-18 [9-21]) s; and from 36.1 (35.1-37.1 [33.0-38.1]) °C to 37.4 (37.0-37.9 [36.0-38.0]) °C, respectively. Contemporary intra-operative resuscitation strategies can normalise the physiological derangements caused by haemorrhagic shock. PMID:23724784

  20. Therapeutic hypothermia achieves neuroprotection via a decrease in acetylcholine with a concurrent increase in carnitine in the neonatal hypoxia-ischemia

    PubMed Central

    Takenouchi, Toshiki; Sugiura, Yuki; Morikawa, Takayuki; Nakanishi, Tsuyoshi; Nagahata, Yoshiko; Sugioka, Tadao; Honda, Kurara; Kubo, Akiko; Hishiki, Takako; Matsuura, Tomomi; Hoshino, Takao; Takahashi, Takao; Suematsu, Makoto; Kajimura, Mayumi

    2015-01-01

    Although therapeutic hypothermia is known to improve neurologic outcomes after perinatal cerebral hypoxia-ischemia, etiology remains unknown. To decipher the mechanisms whereby hypothermia regulates metabolic dynamics in different brain regions, we used a two-step approach: a metabolomics to target metabolic pathways responding to cooling, and a quantitative imaging mass spectrometry to reveal spatial alterations in targeted metabolites in the brain. Seven-day postnatal rats underwent the permanent ligation of the left common carotid artery followed by exposure to 8% O2 for 2.5 hours. The pups were returned to normoxic conditions at either 38°C or 30°C for 3 hours. The brain metabolic states were rapidly fixed using in situ freezing. The profiling of 107 metabolites showed that hypothermia diminishes the carbon biomass related to acetyl moieties, such as pyruvate and acetyl-CoA; conversely, it increases deacetylated metabolites, such as carnitine and choline. Quantitative imaging mass spectrometry demarcated that hypothermia diminishes the acetylcholine contents specifically in hippocampus and amygdala. Such decreases were associated with an inverse increase in carnitine in the same anatomic regions. These findings imply that hypothermia achieves its neuroprotective effects by mediating the cellular acetylation status through a coordinated suppression of acetyl-CoA, which resides in metabolic junctions of glycolysis, amino-acid catabolism, and ketolysis. PMID:25586144

  1. Evolution of Apparent Diffusion Coefficient and Fractional Anisotropy in the Cerebrum of Asphyxiated Newborns Treated with Hypothermia over the First Month of Life.

    PubMed

    Kwan, Saskia; Boudes, Elodie; Benseler, Anouk; Gilbert, Guillaume; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

    2015-01-01

    The objective of this study was to assess the evolution of diffusion-weighted imaging (DWI) and diffusion-tensor imaging (DTI) over the first month of life in asphyxiated newborns treated with hypothermia and to compare it with that of healthy newborns. Asphyxiated newborns treated with hypothermia were enrolled prospectively; and the presence and extent of brain injury were scored on each MRI. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in the basal ganglia, in the white matter and in the cortical grey matter. Sixty-one asphyxiated newborns treated with hypothermia had a total of 126 ADC and FA maps. Asphyxiated newborns developing brain injury eventually had significantly decreased ADC values on days 2-3 of life and decreased FA values around day 10 and 1 month of life compared with those not developing brain injury. Despite hypothermia treatment, asphyxiated newborns may develop brain injury that still can be detected with advanced neuroimaging techniques such as DWI and DTI as early as days 2-3 of life. A study of ADC and FA values over time may aid in the understanding of how brain injury develops in these newborns despite hypothermia treatment. PMID:26229690

  2. Influence of hypothermia and subsequent rewarming upon leukocyte-endothelial interactions and expression of Junctional-Adhesion-Molecules A and B

    PubMed Central

    Bogert, Nicolai V.; Werner, Isabella; Kornberger, Angela; Meybohm, Patrick; Moritz, Anton; Keller, Till; Stock, Ulrich A.; Beiras-Fernandez, Andres

    2016-01-01

    Patients with risks of ischemic injury, e.g. during circulatory arrest in cardiac surgery, or after resuscitation are subjected to therapeutic hypothermia. For aortic surgery, the body is traditionally cooled down to 18 °C and then rewarmed to body temperature. The role of hypothermia and the subsequent rewarming process on leukocyte-endothelial interactions and expression of junctional-adhesion-molecules is not clarified yet. Thus, we investigated in an in-vitro model the influence of temperature modulation during activation and transendothelial migration of leukocytes through human endothelial cells. Additionally, we investigated the expression of JAMs in the rewarming phase. Exposure to low temperatures alone during transmigration scarcely affects leukocyte extravasation, whereas hypothermia during treatment and transendothelial migration improves leukocyte-endothelial interactions. Rewarming causes a significant up-regulation of transmigration with falling temperatures. JAM-A is significantly modulated during rewarming. Our data suggest that transendothelial migration of leukocytes is not only modulated by cell-activation itself. Activation temperatures and the rewarming process are essential. Continued hypothermia significantly inhibits transendothelial migration, whereas the rewarming process enhances transmigration strongly. The expression of JAMs, especially JAM-A, is strongly modulated during the rewarming process. Endothelial protection prior to warm reperfusion and mild hypothermic conditions reducing the difference between hypothermia and rewarming temperatures should be considered. PMID:26912257

  3. The “Neurovascular Unit approach” to Evaluate Mechanisms of Dysfunctional Autoregulation in Asphyxiated Newborns in the era of Hypothermia Therapy

    PubMed Central

    Chalak, Lina F.; Tarumi, Takashi; Zhang, Rong

    2014-01-01

    Despite improvements in obstetrical and neonatal care, and introduction of hypothermia as a neuroprotective therapy, perinatal brain injury remains a frequent cause of cerebral palsy, mental retardation and epilepsy. The recognition of dysfunction of cerebral autoregulation is essential for a real time measure of efficacy to identify those who are at highest risk for brain injury. This article will focus on the “neurovascular unit” approach to the care of asphyxiated neonates to review 1) potential mechanisms of dysfunctional cerebral blood flow (CBF) regulation, 2) optimal monitoring methodology such as NIRS (near infrared spectroscopy), and TCD (transcutaneous Doppler), and 3) clinical implications of monitoring in the neonatal intensive care setting in asphyxiated newborns undergoing hypothermia and rewarming. Critical knowledge of the functional regulation of the neurovascular unit may lead to improved ability to predict outcomes in real time during hypothermia, as well as differentiate nonresponders who might benefit from additional therapies. PMID:25062804

  4. Feasibility Study Evaluating Therapeutic Hypothermia for Refractory Status Epilepticus in Children.

    PubMed

    Buttram, Sandra D W; Au, Alicia K; Koch, Joshua; Lidsky, Karen; McBain, Kristin; O'Brien, Nicole; Zielinski, Brandon A; Bell, Michael J

    2015-12-01

    Pediatric refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality, which lacks consensus regarding diagnosis and treatment(s). Therapeutic hypothermia (TH) is an effective treatment for RSE in preclinical models and small series. In addition, TH is a standard care for adults after cardiac arrest and neonates with hypoxic-ischemic encephalopathy. The purpose of this study was to identify the feasibility of a study of pediatric RSE within a research group (Pediatric Neurocritical Care Research Group [PNCRG]). Pediatric intensive care unit (PICU) admissions at seven centers were prospectively screened from October 2012 to July 2013 for RSE. Experts within the PNCRG estimated that clinicians would be unwilling to enroll a child, unless the child required at least two different antiepileptic medications and a continuous infusion of another antiepileptic medication with ongoing electrographic seizure activity for ≥2 hours after continuous infusion initiation. Data for children meeting the above inclusion criteria were collected, including the etiology of RSE, history of epilepsy, and maximum dose of continuous antiepileptic infusions. There were 8113 PICU admissions over a cumulative 52 months (October 2012-July 2013) at seven centers. Of these, 69 (0.85%) children met inclusion criteria. Twenty children were excluded due to acute diagnoses affected by TH, contraindications to TH, or lack of commitment to aggressive therapies. Sixteen patients had seizure cessation within 2 hours, resulting in 33 patients who had inadequate seizure control after 2 hours and a continuous antiepileptic infusion. Midazolam (21/33, 64%) and pentobarbital (5/33, 15%) were the most common infusions with a wide maximum dose range. More than one infusion was required for seizure control in four patients. There are substantial numbers of subjects at clinical sites within the PNCRG with RSE that would meet the proposed inclusion criteria for a

  5. Immediate prehospital hypothermia protocol in comatose survivors of out-of-hospital cardiac arrest.

    PubMed

    Hammer, Laure; Vitrat, François; Savary, Dominique; Debaty, Guillaume; Santre, Charles; Durand, Michel; Dessertaine, Geraldine; Timsit, Jean-François

    2009-06-01

    Therapeutic hypothermia (TH) improves the outcomes of cardiac arrest (CA) survivors. The aim of this study was to evaluate retrospectively the efficacy and safety of an immediate prehospital cooling procedure implemented just after the return of spontaneous circulation with a prehospital setting. During 30 months, the case records of comatose survivors of out-of-hospital CA presumably due to a cardiac disease were studied. A routine protocol of immediate postresuscitation cooling had been tested by an emergency team, which consisted of an infusion of large-volume, ice-cold intravenous saline. We decided to assess the efficacy and tolerance of this procedure. A total of 99 patients were studied; 22 were treated with prehospital TH, and 77 consecutive patients treated with prehospital standard resuscitation served as controls. For all patients, TH was maintained for 12 to 24 hours. The demographic, clinical, and biological characteristics of the patients were similar in the 2 groups. The rate of patients with a body temperature of less than 35 degrees C upon admission was 41% in the cooling group and 18% in the control group. Rapid infusion of fluid was not associated with pulmonary edema. After 1 year of follow-up, 6 (27%) of 22 patients in the cooling group and 30 (39%) of 77 patients in the control group had a good outcome. Our preliminary observation suggests that in comatose survivors of CA, prehospital TH with infusion of large-volume, ice-cold intravenous saline is feasible and can be used safely by mobile emergency and intensive care units. PMID:19497463

  6. Prolonged hypothermia exposure diminishes neuroprotection for severe ischemic-hypoxic primary neurons.

    PubMed

    Gao, Xiao-Ya; Zhu, Shu-Zhen; Xiang, Wei; Huang, Kai-Bin; Hu, Ya-Fang; Gu, Yong; Pan, Su-Yue

    2016-04-01

    This study aimed to identify optimal mild hypothermic (MH) condition that would provide the best protection for neuronal cells undergoing severe ischemia and hypoxia. We also sought to determine if longer exposure to mild hypothermia would confer greater protection to severe ischemia and hypoxia in these cells. We designed a primary neuronal cell model for severe glucose and oxygen deprivation/reoxygenation (OGD/R) to simulate the hypoxic-ischemic condition of patients with severe stroke, trauma, or hypoxic-ischemic encephalopathy. We evaluated the viability of these neurons following 3 h of OGD/R and variable MH conditions including different temperatures and durations of OGD/R exposure. We further explored the effects of the optimal MH condition on several parts which are associated with mitochondrial apoptosis pathway: intracellular calcium, reactive oxygen species (ROS), and mitochondrial transmembrane potential (MTP). The results of this study showed that the apoptosis proportion (AP) and cell viability proportion (CVP) after OGD/R significantly varied depending on which MH condition cells were exposed to (p < 0.001). Further, our findings showed that prolonged MH reduced the neuroprotection to AP and CVP. We also determined that the optimal MH conditions (34 °C for 4.5 h) reduced intracellular calcium, ROS, and recovered MTP. These findings indicate that there is an optimal MH treatment strategy for severely hypoxia-ischemic neurons, prolonged duration might diminish the neuroprotection, and that MH treatment likely initiates neuroprotection by inhibiting the mitochondrial apoptosis pathway. PMID:26802735

  7. Treatment temperature and insult severity influence the neuroprotective effects of therapeutic hypothermia

    PubMed Central

    Wood, Thomas; Osredkar, Damjan; Puchades, Maja; Maes, Elke; Falck, Mari; Flatebø, Torun; Walløe, Lars; Sabir, Hemmen; Thoresen, Marianne

    2016-01-01

    Therapeutic hypothermia (HT) is standard care for moderate and severe neonatal hypoxic-ischaemic encephalopathy (HIE), the leading cause of permanent brain injury in term newborns. However, the optimal temperature for HT is still unknown, and few preclinical studies have compared multiple HT treatment temperatures. Additionally, HT may not benefit infants with severe encephalopathy. In a neonatal rat model of unilateral hypoxia-ischaemia (HI), the effect of five different HT temperatures was investigated after either moderate or severe injury. At postnatal-day seven, rat pups underwent moderate or severe HI followed by 5 h at normothermia (37 °C), or one of five HT temperatures: 33.5 °C, 32 °C, 30 °C, 26 °C, and 18 °C. One week after treatment, neuropathological analysis of hemispheric and hippocampal area loss, and CA1 hippocampal pyramidal neuron count, was performed. After moderate injury, a significant reduction in hemispheric and hippocampal loss on the injured side, and preservation of CA1 pyramidal neurons, was seen in the 33.5 °C, 32 °C, and 30 °C groups. Cooling below 33.5 °C did not provide additional neuroprotection. Regardless of treatment temperature, HT was not neuroprotective in the severe HI model. Based on these findings, and previous experience translating preclinical studies into clinical application, we propose that milder cooling should be considered for future clinical trials. PMID:26997257

  8. Psychotropic drug-associated electrocardiographic presentation of diffuse J-waves in hypothermia: case report and literature review.

    PubMed

    Kataoka, Hajime; Kajiwara, Hirofumi; Yano, Eiji

    2016-06-01

    The use of psychotropic drugs is often associated with electrocardiographic (ECG) QT-interval prolongation, but there are few reports of J-waves. This report describes the case of a schizophrenic patient under treatment with several psychotropic drugs (olanzapine, valproate, and flunitrazepam), in whom ECG J-waves diffusely appeared during a hypothermic episode. We further performed a literature review of psychotropic drug-related J-waves in hypothermia. The present case highlights the importance of recognizing psychotropic drug-related ECG J-waves on an early warning sign to ensure appropriate monitoring and/or treatment for possible life-threatening side effects of such medications. PMID:25666953

  9. Apoplastic sugars and cell-wall invertase are involved in formation of the tolerance of cold-resistant potato plants to hypothermia.

    PubMed

    Deryabin, A N; Burakhanova, E A; Trunova, T I

    2015-01-01

    We studied the involvement of apoplastic sugars (glucose, fructose, and sucrose) and the cell-wall invertase (CWI) in the formation of the tolerance of cold-resistant potato plants (Solanum tuberosum L., cv Désirée) to hypothermia. The activity of CW1 and the content in the cell and the apoplast substrate (sucrose) and the reaction products of this enzyme (glucose and fructose) have a significant influence on the formation of the tolerance of cold-resistant potato plants to hypothermia. PMID:26728726

  10. Methods for study of cardiovascular adaptation of small laboratory animals during exposure to altered gravity. [hypothermia for cardiovascular control and cancer therapy

    NASA Technical Reports Server (NTRS)

    Popovic, V.

    1973-01-01

    Several new techniques are reported for studying cardiovascular circulation in small laboratory animals kept in metabolic chambers. Chronical cannulation, miniaturized membrane type heart-lung machines, a prototype walking chamber, and a fluorocarbon immersion method to simulate weightlessness are outlined. Differential hypothermia work on rat cancers provides localized embedding of radionuclides and other chemotherapeutical agents in tumors and increases at the same time blood circulation through the warmed tumor as compared to the rest of the cold body. Some successful clinical applications of combined chemotherapy and differential hypothermia in skin cancer, mammary tumors, and brain gliomas are described.

  11. A case of transient hypothermia after trans-lamina terminalis and third ventricle clipping of an extremely high-position basilar tip aneurysm

    PubMed Central

    Ikawa, Fusao; Hamasaki, Osamu; Kurokawa, Yasuharu; Yonezawa, Ushio; Kurisu, Kaoru

    2015-01-01

    Reports on the trans-lamina terminalis and trans-third ventricular approach are rare. The risk associated with this approach is unknown. After an unsuccessful endovascular surgery, we performed direct surgical clipping via the third ventricle on a 78-year-old woman presenting with an extremely high-positioned, ruptured basilar tip aneurysm. She experienced transient hypothermia for 5 days, and it was considered that this was due to hypothalamic dysfunction. It is necessary to recognize that there is the potential for hypothermia after surgery via the lamina terminalis and third ventricle, even though the mechanisms of hypothalamic thermoregulation are still unclear. PMID:27489684

  12. First Use of a New Device for Administration of Buspirone and Acetaminophen to Suppress Shivering During Therapeutic Hypothermia.

    PubMed

    Honasoge, Akilesh; Parker, Braden; Wesselhoff, Kelly; Lyons, Neal; Kulstad, Erik

    2016-03-01

    Therapeutic hypothermia or targeted temperature management has been used after cardiac arrest to improve neurological outcomes and mortality. However, a side effect of temperature modulation is a centrally mediated shivering response. The Columbia Anti-Shivering Protocol sets up a systematic method of intravenous (IV) and oral medication escalation to suppress this response and preserve the benefits of this therapy. We present the case of a 59-year-old male who began shivering after therapeutic hypothermia for cardiac arrest, leading to a persistent rise in core temperature despite adequate sedation. He was also found to have gastric contents similar to coffee grounds through nasogastric tube suction. The shivering was effectively suppressed and the rising core temperature plateaued using rectal acetaminophen and buspirone administered by means of a novel device, the Macy Catheter. Also, when used in conjunction with other protocol-driven medications, the patient was able to achieve a core temperature of 33°C. The Macy Catheter appears to be a useful approach to rectally administer buspirone and acetaminophen, using an easy-to-place, nonsterile atraumatic device that requires no radiographic confirmation of placement. PMID:26807775

  13. First Use of a New Device for Administration of Buspirone and Acetaminophen to Suppress Shivering During Therapeutic Hypothermia

    PubMed Central

    Parker, Braden; Wesselhoff, Kelly; Lyons, Neal; Kulstad, Erik

    2016-01-01

    Therapeutic hypothermia or targeted temperature management has been used after cardiac arrest to improve neurological outcomes and mortality. However, a side effect of temperature modulation is a centrally mediated shivering response. The Columbia Anti-Shivering Protocol sets up a systematic method of intravenous (IV) and oral medication escalation to suppress this response and preserve the benefits of this therapy. We present the case of a 59-year-old male who began shivering after therapeutic hypothermia for cardiac arrest, leading to a persistent rise in core temperature despite adequate sedation. He was also found to have gastric contents similar to coffee grounds through nasogastric tube suction. The shivering was effectively suppressed and the rising core temperature plateaued using rectal acetaminophen and buspirone administered by means of a novel device, the Macy Catheter. Also, when used in conjunction with other protocol-driven medications, the patient was able to achieve a core temperature of 33°C. The Macy Catheter appears to be a useful approach to rectally administer buspirone and acetaminophen, using an easy-to-place, nonsterile atraumatic device that requires no radiographic confirmation of placement. PMID:26807775

  14. The Next Generation of Cold Immersion Dry Suit Design Evolution for Hypothermia Prevention

    NASA Technical Reports Server (NTRS)

    Galofaro, Joel

    2013-01-01

    This new utility patent is an active design that relies on the lung's role as an organic heat exchanger for providing deep body core heating of air. It is based on the fact that the greatest heat loss mechanism for an insulated human body immersed in a cold water environment is due to heat loss through respiration. This innovation successfully merges two existing technologies (cold immersion suit and existing valve technologies) to produce a new product that helps prevent against the onset of hypothermia at sea. During normal operations, a human maintains an approximate body temperature of [98.6 F (37 C)]. A mechanism was developed to recover the warm temperature from the body and reticulate it in a survival suit. The primary intention is to develop an encompassing systems design that can both easily and cost effectively be integrated in all existing currently manufactured cold water survival suits, and as such, it should be noted that the cold water immersion suit is only used as a framework or tool for laying out the required design elements. At the heart of the suit is the Warm Air Recovery (WAR) system, which relies on a single, large Main Purge Valve (MPV) and secondary Purge Valves (PV) to operate. The main purge valve has a thin membrane, which is normally closed, and acts as a one-way check valve. When warm air is expelled from the lungs, it causes the main purge valve to open. Air forced from the MPV is dumped directly into the suit, thereby providing warmth to the torso, legs, and arms. A slight positive over-pressure in the suit causes warm waste air (or water if the suit is punctured) to be safely vented into the sea through large PVs located at the bottom of each arm and leg. The secondary purge valves act to prevent the buildup of large concentrations of CO2 gas and help guard against asphyxia. It is noted that the MPV causes the inhalation and exhalation cycles to be completely isolated from one another in the current suit design.

  15. Factors influencing survival of mammalian cells exposed to hypothermia. VI. Effects of prehypothermic hypoxia followed by aerobic or hypoxic storage at various hypothermic temperatures.

    PubMed

    Kruuv, J; Lepock, J R

    1995-04-01

    The Arrhenius plot of inactivation (killing) rates of V-79 Chinese hamster cells exposed to hypothermia in air-equilibrated (aerobic) medium contains a break at about 8 degrees C, which corresponds to the minimum inactivation rate, implying that there are distinct hypothermic damage mechanisms above (range I, 8 to 25 degrees C) and below (range II, 0 to 8 degrees C) 8 degrees C. Prehypothermic hypoxia (PHH) for 75 min at room temperature sensitizes cells to subsequent aerobic hypothermia at both 5 and 10 degrees C (range II and I). However, PHH followed by severe hypoxia (0.03 microM oxygen in the medium) protected cells during 10 degrees C (range I) storage by increasing the shoulder, but not the slope, of the cell survival curve compared to the PHH plus 10 degrees C aerobic hypothermia case. On the other hand, PHH plus severe hypoxia during 5 degrees C storage (range II) protected cells by decreasing the slope, but not the shoulder, of the cell survival curve compared to the PHH plus 5 degrees C aerobic hypothermia case. Furthermore, PHH plus severe hypoxia during 5 degrees C storage was not significantly worse than aerobic storage without PHH at 5 degrees C. With or without severe hypoxia, 10 degrees C storage is preferable to 5 degrees C storage in this cell line. Extrapolated to organ storage, the results may imply that if warm ischemia (PHH) has occurred, subsequent hypoxic hypothermic perfusion storage may be preferable to aerobic hypothermic perfusion storage. PMID:7743821

  16. Neuroprotective effect of N-acetyl-aspartyl-glutamate in combination with mild hypothermia in the endothelin-1 rat model of focal cerebral ischaemia.

    PubMed

    Van Hemelrijck, An; Hachimi-Idrissi, Said; Sarre, Sophie; Ebinger, Guy; Michotte, Yvette

    2005-12-01

    Previously we showed that treatment with mild hypothermia (34 degrees C for 2 h) after a focal cerebral infarct was neuroprotective by reducing apoptosis in the penumbra (cortex), but not in the core (striatum) of the infarct. In this study we examined whether administration of N-acetyl-aspartyl-glutamate (NAAG) in combination with mild hypothermia could improve striatal neuroprotection in the endothelin-1 rat model. NAAG (10 mg/kg i.p.) was injected under normothermic (37 degrees C) or mild hypothermic conditions, either 40 min before or 20 min after the insult. NAAG reduced caspase 3 immunoreactivity in the striatum, irrespective of the time of administration and brain temperature. This neuroprotective effect could be explained, at least partially, by decreased nitric oxide synthase activity in the striatum and was blocked by the group II metabotropic glutamate receptor antagonist, LY341495. Hypothermia applied together with NAAG reduced both cortical and striatal caspase 3 immunoreactivity, as well as the overall ischaemic damage in these areas. However, no pronounced improvement was seen in total damaged brain volume. Extracellular glutamate levels did not correlate with the observed protection, whatever treatment protocol was applied. We conclude that treatment with NAAG causes the same degree of neuroprotection as treatment with hypothermia. Combination of the two treatments, although reducing apoptosis, does not considerably improve ischaemic damage. PMID:16135071

  17. A recommended early goal-directed management guideline for the prevention of hypothermia-related transfusion, morbidity, and mortality in severely injured trauma patients.

    PubMed

    Perlman, Ryan; Callum, Jeannie; Laflamme, Claude; Tien, Homer; Nascimento, Barto; Beckett, Andrew; Alam, Asim

    2016-01-01

    Hypothermia is present in up to two-thirds of patients with severe injury, although it is often disregarded during the initial resuscitation. Studies have revealed that hypothermia is associated with mortality in a large percentage of trauma cases when the patient's temperature is below 32 °C. Risk factors include the severity of injury, wet clothing, low transport unit temperature, use of anesthesia, and prolonged surgery. Fortunately, associated coagulation disorders have been shown to completely resolve with aggressive warming. Selected passive and active warming techniques can be applied in damage control resuscitation. While treatment guidelines exist for acidosis and bleeding, there is no evidence-based approach to managing hypothermia in trauma patients. We synthesized a goal-directed algorithm for warming the severely injured patient that can be directly incorporated into current Advanced Trauma Life Support guidelines. This involves the early use of warming blankets and removal of wet clothing in the prehospital phase followed by aggressive rewarming on arrival at the hospital if the patient's injuries require damage control therapy. Future research in hypothermia management should concentrate on applying this treatment algorithm and should evaluate its influence on patient outcomes. This treatment strategy may help to reduce blood loss and improve morbidity and mortality in this population of patients. PMID:27095272

  18. The effects of therapeutic hypothermia on cerebral metabolism in neonates with hypoxic-ischemic encephalopathy: An in vivo 1H-MR spectroscopy study.

    PubMed

    Wisnowski, Jessica L; Wu, Tai-Wei; Reitman, Aaron J; McLean, Claire; Friedlich, Philippe; Vanderbilt, Douglas; Ho, Eugenia; Nelson, Marvin D; Panigrahy, Ashok; Blüml, Stefan

    2016-06-01

    Therapeutic hypothermia has emerged as the first empirically supported therapy for neuroprotection in neonates with hypoxic-ischemic encephalopathy (HIE). We used magnetic resonance spectroscopy ((1)H-MRS) to characterize the effects of hypothermia on energy metabolites, neurotransmitters, and antioxidants. Thirty-one neonates with HIE were studied during hypothermia and after rewarming. Metabolite concentrations (mmol/kg) were determined from the thalamus, basal ganglia, cortical grey matter, and cerebral white matter. In the thalamus, phosphocreatine concentrations were increased by 20% during hypothermia when compared to after rewarming (3.49 ± 0.88 vs. 2.90 ± 0.65, p < 0.001) while free creatine concentrations were reduced to a similar degree (3.00 ± 0.50 vs. 3.74 ± 0.85, p < 0.001). Glutamate (5.33 ± 0.82 vs. 6.32 ± 1.12, p < 0.001), aspartate (3.39 ± 0.66 vs. 3.87 ± 1.19, p < 0.05), and GABA (0.92 ± 0.36 vs. 1.19 ± 0.41, p < 0.05) were also reduced, while taurine (1.39 ± 0.52 vs. 0.79 ± 0.61, p < 0.001) and glutathione (2.23 ± 0.41 vs. 2.09 ± 0.33, p < 0.05) were increased. Similar patterns were observed in other brain regions. These findings support that hypothermia improves energy homeostasis by decreasing the availability of excitatory neurotransmitters, and thereby, cellular energy demand. PMID:26661180

  19. Neuroprotective effect of therapeutic hypothermia versus standard care alone after convulsive status epilepticus: protocol of the multicentre randomised controlled trial HYBERNATUS.

    PubMed

    Legriel, Stephane; Pico, Fernando; Tran-Dinh, Yves-Roger; Lemiale, Virginie; Bedos, Jean-Pierre; Resche-Rigon, Matthieu; Cariou, Alain

    2016-12-01

    Convulsive status epilepticus (CSE) is a major medical emergency associated with a 50 % morbidity rate. CSE guidelines have recommended prompt management for many years, but there is no evidence to date that they have significantly improved practices or outcomes. Developing neuroprotective strategies for use after CSE holds promise for diminishing morbidity and mortality rates. Hypothermia has been shown to afford neuroprotection in various health conditions. We therefore designed a trial to determine whether 90-day outcomes in mechanically ventilated patients with CSE requiring management in the intensive care unit (ICU) are improved by early therapeutic hypothermia (32-34 °C) for 24 h with propofol sedation. We are conducting a multicentre, open-label, parallel-group, randomised, controlled trial (HYBERNATUS) of potential neuroprotective effects of therapeutic hypothermia and routine propofol sedation started within 8 h after CSE onset in ICU patients requiring mechanical ventilation. Included patients are allocated to receive therapeutic hypothermia (32-34 °C) plus standard care or standard care alone. We plan to enrol 270 patients in 11 ICUs. An interim analysis is scheduled after the inclusion of 135 patients. The main study objective is to evaluate the effectiveness of therapeutic hypothermia (32-34 °C) for 24 h in diminishing 90-day morbidity and mortality (defined as a Glasgow Outcome Scale score <5). The HYBERNATUS trial is expected to a decreased proportion of patients with a Glasgow Outcome Scale score lower than 5 after CSE requiring ICU admission and mechanical ventilation. Trial registration Clinicaltrials.gov identifier NCT01359332 (registered on 23 May 2011). PMID:27325409

  20. Clinical experience with an active intravascular rewarming technique for near-severe hypothermia associated with traumatic injury.

    PubMed

    Kiridume, Kazutaka; Hifumi, Toru; Kawakita, Kenya; Okazaki, Tomoya; Hamaya, Hideyuki; Shinohara, Natsuyo; Abe, Yuko; Takano, Koshiro; Hagiike, Masanobu; Kuroda, Yasuhiro

    2014-01-01

    Hypothermia and acidosis are secondary causes of trauma-related coagulopathy. Here we report the case of a 72-year-old patient with severe trauma who suffered near-severe hypothermia despite the initiation of standard warming measures and was successfully managed with active intravascular rewarming. The patient was involved in a road traffic accident and was transported to a hospital. He was diagnosed with massive right-sided hemothorax, blunt aortic injury, burst fractures of the eighth and ninth thoracic vertebrae, and open fracture of the right tibia. He was referred to our hospital, where emergency surgery was performed to control bleeding from the right hemothorax. During surgery, the patient demonstrated progressive heat loss despite standard rewarming measures, and his temperature decreased to 32.4°C. Severe acidosis was also observed. A Cool Line® catheter was inserted into the right femoral vein and lodged in the inferior vena cava, and an intravascular balloon catheter system was utilized for aggressive rewarming. The automated target core temperature was set at 37°C, and the maximum flow rate was used. His core temperature reached 36.0°C after 125 min of intravascular rewarming. The severe acidosis was also resolved. The main active bleeding site was not identified, and coagulation hemostasis as well as rewarming enabled us to control bleeding from the vertebral bodies, lung parenchyma, and pleura. The total volume of intraoperative bleeding was 5,150 mL, and 20 units of red cell concentrate and 16 units of fresh frozen plasma were transfused. After surgery, he was transferred to the intensive care unit under endotracheal intubation and mechanical ventilation. His hemodynamic condition stabilized after surgery. The rewarming catheter was removed on day 2 of admission, and no bleeding, infection, or thrombosis associated with catheter placement was observed. Extubation was performed on day 40, and his subsequent clinical course was uneventful. He

  1. Potentiation of phenobarbital-induced anticonvulsant activity by pipecolic acid.

    PubMed

    Takahama, K; Miyata, T; Okano, Y; Kataoka, M; Hitoshi, T; Kasé, Y

    1982-07-01

    Pipecolic acid (PA) is an intermediate of lysine metabolism in the mammalian brain. Recent findings suggest a functional connection of PA as neuromodulator in GABAergic transmission. Since many drugs are postulated to produce their effects by interaction with the central GABA system, the influence of PA on the anticonvulsant activity of phenobarbital was examined. Pretreatment of mice with 50 mg . kg-1 of PA potentiated the suppressing effects of the barbiturate on electrically and chemically induced convulsions. However, there was no potentiation of the behavioral effects and hypothermia induced by phenobarbital. PA itself had no or only little effect on the convulsions, motor function and rectal temperature when given in i.p. doses up to 500 mg . kg-1. Intraventricular administration of 500 microgram of PA also did not suppress either type of convulsion, although it produced ptosis, hypotonia, sedation and hypothermia. The results are discussed in relation to GABA system. PMID:6288409

  2. The Use of Pre-Hospital Mild Hypothermia after Resuscitation from Out-of-Hospital Cardiac Arrest

    PubMed Central

    Olsufka, Michele; Nichol, Graham; Copass, Michael K.; Cobb, Leonard A.

    2009-01-01

    Abstract Hypothermia has emerged as a potent neuroprotective modality following resuscitation from cardiac arrest. Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling begun immediately following the return of spontaneous circulation may be more beneficial. Cooling in the field following resuscitation, however, presents new challenges, in that the cooling method has to be portable, safe, and effective. Rapid infusion of intravenous fluid at 4°C, the use of a cooling helmet, and cooling plates have all been proposed as methods for field cooling, and are all in various stages of clinical and animal testing. Whether field cooling will improve survival and neurologic outcome remains an important unanswered clinical question. PMID:19072587

  3. The use of pre-hospital mild hypothermia after resuscitation from out-of-hospital cardiac arrest.

    PubMed

    Kim, Francis; Olsufka, Michele; Nichol, Graham; Copass, Michael K; Cobb, Leonard A

    2009-03-01

    Hypothermia has emerged as a potent neuroprotective modality following resuscitation from cardiac arrest. Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling begun immediately following the return of spontaneous circulation may be more beneficial. Cooling in the field following resuscitation, however, presents new challenges, in that the cooling method has to be portable, safe, and effective. Rapid infusion of intravenous fluid at 4 degrees C, the use of a cooling helmet, and cooling plates have all been proposed as methods for field cooling, and are all in various stages of clinical and animal testing. Whether field cooling will improve survival and neurologic outcome remains an important unanswered clinical question. PMID:19072587

  4. Induction of therapeutic hypothermia after cardiac arrest in prehospital patients using ice-cold Ringer's solution: a pilot study.

    PubMed

    Virkkunen, Ilkka; Yli-Hankala, Arvi; Silfvast, Tom

    2004-09-01

    The cooling and haemodynamic effects of prehospital infusion of ice-cold Ringer's solution were studied in 13 adult patients after successful resuscitation from non-traumatic cardiac arrest. After haemodynamics stabilisation, 30 ml/kg of Ringer's solution was infused at a rate of 100ml/min into the antecubital vein. Arterial blood pressure and blood gases, pulse rate, end-tidal CO(2) and oesophageal temperature were monitored closely. The mean core temperature decreased from 35.8 +/- 0.9 degrees C at the start of infusion to 34.0 +/- 1.2 degrees C on arrival at hospital (P < 0.0001). No serious adverse haemodynamic effects occurred. It is concluded that the induction of therapeutic hypothermia using this technique in the prehospital setting is feasible. PMID:15325449

  5. [The neuroprotective effect of mild therapeutic hypothermia after out-of-hospital cardiac arrest with successful reanimation - a case report].

    PubMed

    Szczygieł, Jarosław; Mazurek, Justyna; Świątkowski, Andrzej; Broniec-Siekaniec, Katarzyna; Czapnik, Marta; Średniawa, Beata; Opara, Józef; Oleszczyk, Krystian

    2016-03-01

    The use of mild therapeutic hypothermia (MTH) in adult patients remaining in a coma following cardiac arrest, regardless of its mechanism and location, is recommended by the European Resuscitation Council. The study presents a case of a 52-year-old man in whom MTH was used following successfully resuscitated out-of- hospital sudden cardiac arrest caused by ventricular fibrillation. On the basis of this case it was indicated that the use of low temperatures may be an effective method of neuroprotective treatment since such activity is compatible with later observed great possibility of the brain to compensate and with the maintenance of brain plasticity which is crucial for neuropsychological rehabilitation. PMID:27088200

  6. Endogenous hypothermic response to hypoxia reduces brain injury: Implications for modeling hypoxic-ischemic encephalopathy and therapeutic hypothermia in neonatal mice.

    PubMed

    Reinboth, Barbara S; Köster, Christian; Abberger, Hanna; Prager, Sebastian; Bendix, Ivo; Felderhoff-Müser, Ursula; Herz, Josephine

    2016-09-01

    Hypothermia treatment (HT) is the only formally endorsed treatment recommended for hypoxic-ischemic encephalopathy (HIE). However, its success in protecting against brain injury is limited with a number to treat of 7-8. The identification of the target mechanisms of HIE in combination with HT will help to explain ineffective therapy outcomes but also requires stable experimental models in order to establish further neuroprotective therapies. Despite clinical and experimental indications for an endogenous thermoregulatory response to HIE, the potential effects on HIE-induced brain injury have largely been neglected in pre-clinical studies. In the present study we analyzed gray and white matter injury and neurobehavioral outcome in neonatal mice considering the endogenous thermoregulatory response during HIE combined with HT. HIE was induced in postnatal day (PND) 9 C57BL/6 mice through occlusion of the right common carotid artery followed by one hour of hypoxia. Hypoxia was performed at 8% or 10% oxygen (O2) at two different temperatures based on the nesting body core temperature. Using the model which mimics the clinical situation most closely, i.e. through maintenance of the nesting temperature during hypoxia we compared two mild HT protocols (rectal temperature difference 3°C for 4h), initiated either immediately after HIE or with delay of 2h. Injury was determined by histology, immunohistochemistry and western blot analyses at PND 16 and PND 51. Functional outcome was evaluated by Rota Rod, Elevated Plus Maze, Open Field and Novel Object Recognition testing at PND 30-PND 36 and PND 44-PND 50. We show that HIE modeling in neonatal mice is associated with a significant endogenous drop in body core temperature by 2°C resulting in profound neuroprotection, expressed by reduced neuropathological injury scores, reduced loss of neurons, axonal structures, myelin and decreased astrogliosis. Immediately applied post-hypoxic HT revealed slight advantages over a delayed

  7. Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic–ischemic pig model

    PubMed Central

    Chakkarapani, Elavazhagan; Dingley, John; Aquilina, Kristian; Osredkar, Damjan; Liu, Xun; Thoresen, Marianne

    2013-01-01

    Autoregulation of cerebral perfusion is impaired in hypoxic–ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between −1 and +1, is impaired during and after a hypoxic–ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx >0.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as ‘severe' or ‘mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P=0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, −0.098 (95% CI (−0.18, −0.01)), independent of the insult severity. PMID:23899927

  8. [A comparative analysis of restoration of electroencephalographic and protein-synthesizing activities in neocortex and hippocampus in hibernating (ground squirrels) and nonhibernating (rats) animals during exit from hypothermia].

    PubMed

    Ignat'ev, D A; Gordon, R Ia; Vorob'ev, V V; Rogachevskiĭ, V V

    2005-01-01

    A similarity in the sequence of restoration of the EEG spectrum between ground squirrels arousing from torpor and rats passing out of artificial hypothermia (17-18 degrees C) was shown. First of all, the low-frequency part of the EEG spectrum was restored. As animals warmed up, their breathing became hurried, cold shivering appeared, and the theta- and alpha-rhythms increased. During the exit from hypothermia, the activity of the protein-synthesizing system in both rats and ground squirrels was almost entirely restored when the animal body temperature achieved 21-22 degrees C. In ground squirrel, the rate of protein synthesis in the neocortex was lower than in hippocampus CA1 and CA3 areas, whereas in rats, on the contrary, it was higher in the neocortex in comparison with the CA3 area. PMID:15759514

  9. Predictive value of the amplitude integrated EEG in infants with hypoxic ischaemic encephalopathy: data from a randomised trial of therapeutic hypothermia

    PubMed Central

    Azzopardi, Denis

    2014-01-01

    The amplitude integrated EEG (aEEG) is reputed to be one of the best predictors of neurological outcome following hypoxic ischaemic encephalopathy in term newborns and was used to select infants into trials of neuroprotection with hypothermia, but its predictive value and the effect of moderate hypothermia on the aEEG have not previously been examined in a randomised study. The positive predictive value (PPV) of the aEEG recorded within 6 h of birth for death or disability at 18 months of age was determined in 314 infants born after 35 weeks gestation who were randomised to receive standard care with or without cooling for 72 h. The aEEG was classified according to voltage and by pattern. The PPV of a severely abnormal aEEG assessed by the voltage and pattern methods was 0.63 and 0.59 respectively in non-cooled infants and 0.55 and 0.51 in cooled infants (p>0.05). Although the differences in PPV between cooled and non-cooled groups were not significant, they are consistent with observational studies showing a lower PPV in infants treated with hypothermia, probably due to a neuroprotective effect of cooling. PMID:23800393

  10. Therapeutic Hypothermia for Refractory Status Epilepticus in a Child with Malignant Migrating Partial Seizures of Infancy and SCN1A Mutation: A Case Report

    PubMed Central

    Shein, Steven L.; Reynolds, Thomas Q.; Gedela, Satyanarayana; Kochanek, Patrick M.

    2012-01-01

    Status epilepticus (SE) is a common indication for neurocritical care and can be refractory to standard measures. Refractory SE (RSE) is associated with high morbidity and mortality. Unconventional therapies may be utilized in certain cases, including therapeutic hypothermia (TH), bumetanide, and the ketogenic diet. However, the literature describing the use of such therapies in RSE is limited. Details of a case of TH for RSE in an infant with malignant migrating partial seizures of infancy were obtained from the medical record. A 4-month-old child developed SE that was refractory to treatment with concurrent midazolam, phenobarbital, fosphenytoin, topiramate, levetiracetam, folinic acid, and pyridoxal-5-phosphate. This led to progressive implementation of three unconventional therapies: TH, bumetanide, and the ketogentic diet. Electrographic seizures ceased for the entirety of a 43-hour period of TH with a target rectal temperature of 33.0°C–34.0°C. No adverse effects of hypothermia were noted other than a single episode of asymptomatic hypokalemia. Seizures recurred 10 hours after rewarming was begun and did not abate with reinstitution of hypothermia. No effect was seen with administration of bumetanide. Seizures were controlled long-term within 48 hours of institution of the ketogenic diet. TH and the ketogenic diet may be effective for treating RSE in children. PMID:23667778

  11. Fever After Rewarming: Incidence of Pyrexia in Post-Cardiac Arrest Patients who have Undergone Mild Therapeutic Hypothermia

    PubMed Central

    Cocchi, Michael N.; Boone, Myles D.; Giberson, Brandon; Giberson, Tyler; Farrell, Emily; Salciccioli, Justin D.; Talmor, Daniel; Williams, Donna; Donnino, Michael W.

    2014-01-01

    Background Induction of mild therapeutic hypothermia, or TH (temperature 32–34°C), has become standard of care in many hospitals for comatose survivors of cardiac arrest. Pyrexia, or fever, is known to be detrimental in patients with neurologic injuries such as stroke or trauma. The incidence of pyrexia in the post-rewarming phase of TH is unknown. We attempted to determine the incidence of fever after TH, and hypothesized that those patients who were febrile after rewarming would have worse clinical outcomes than those who maintained normothermia in the post-rewarming period. Methods Retrospective data analysis of survivors of out-of-hospital cardiac arrest (OHCA) over a period of 29 months (12/2007–4/2010). Inclusion criteria: OHCA, age > 18, return of spontaneous circulation (ROSC), and treatment with TH. Exclusion criteria: traumatic arrest, pregnancy. Data collected included age, sex, neurologic outcome, mortality, and whether the patient developed a fever (temperature > 100.4°F, 38°C) within 24 hours after being fully rewarmed to a normal core body temperature after TH. We used simple descriptive statistics and Fisher’s exact test to report our findings. Results A total of 149 patients were identified; of these, 82 (55%) underwent TH. The mean age of the TH cohort was 66 years, and 28 (31%) were female. 54 patients survived for > 24 hours after rewarming and were included in the analysis. Among the analyzed cohort, 28/54 (52 %) developed fever within 24 hours after being rewarmed. Outcome measures included in-hospital mortality, as well as neurologic outcome as defined by a dichotomized Cerebral Performance Category (CPC) score. 1, 2 When comparing neurologic outcomes between the groups, 16/28 (57%) in the post-rewarming fever group had a poor outcome (CPC score 3–5), while 15/26 (58%) in the no-fever group had a favorable outcome (P=0.62). In the fever group, 15/28 (52%) died, while in the no-fever group, 14/26 (54%) died (P=0.62). Conclusion

  12. Environmental conditions at the South Col of Mount Everest and their impact on hypoxia and hypothermia experienced by mountaineers

    PubMed Central

    2012-01-01

    Background Hypoxia and hypothermia are acknowledged risk factors for those who venture into high-altitude regions. There is, however, little in situ data that can be used to quantify these risks. Here, we use 7 months of continuous meteorological data collected at the South Col of Mount Everest (elevation 7,896 m above sea level) to provide the first in situ characterization of these risks near the summit of Mount Everest. Methods This is accomplished through the analysis of barometric pressure, temperature and wind speed data collected by an automatic weather station installed at the South Col. These data were also used as inputs to parameterizations of wind chill equivalent temperature (WCT) and facial frostbite time (FFT). Results The meteorological data show clear evidence of seasonality, with evidence of pre-monsoon, monsoon and post-monsoon conditions. Low pressures, cold temperatures and high wind speeds characterize the pre- and post-monsoon periods with significant variability associated with the passage of large-scale weather systems. In contrast, the monsoon period is characterized by higher pressures, warmer temperatures and lower wind speeds with a pronounced reduction in variability. These environmental conditions are reflected in WCTs as low as −50°C and FFTs as short as 2 min during the pre- and post-monsoon periods. During the monsoon, the risk of cold injury is reduced with WCTs of order −20°C and FFTs longer than 60 min. The daily cycle in the various parameters is also investigated in order to assess the changes in conditions that would be experienced during a typical summit day. The post-monsoon period in particular shows a muted daily cycle in most parameters that is proposed to be the result of the random timing of large-scale weather systems. Conclusions Our results provide the first in situ characterization of the risk of hypoxia and hypothermia on Mount Everest on daily, weekly and seasonal timescales, and provide additional

  13. Brain tissue partial pressure of oxygen predicts the outcome of severe traumatic brain injury under mild hypothermia treatment

    PubMed Central

    Sun, Hongtao; Zheng, Maohua; Wang, Yanmin; Diao, Yunfeng; Zhao, Wanyong; Wei, Zhengjun

    2016-01-01

    Objective The aim of this study was to investigate the clinical significance and changes of brain tissue partial pressure of oxygen (PbtO2) in the course of mild hypothermia treatment (MHT) for treating severe traumatic brain injury (sTBI). Methods There were 68 cases with sTBI undergoing MHT. PbtO2, intracranial pressure (ICP), jugular venous oxygen saturation (SjvO2), and cerebral perfusion pressure (CPP) were continuously monitored, and clinical outcomes were evaluated using the Glasgow Outcome Scale score. Results Of 68 patients with sTBI, PbtO2, SjvO2, and CPP were obviously increased, but decreased ICP level was observed throughout the MHT. PbtO2 and ICP were negatively linearly correlated, while there was a positive linear correlation between PbtO2 and SjvO2. Monitoring CPP and SjvO2 was performed under normal circumstances, and a large proportion of patients were detected with low PbtO2. Decreased PbtO2 was also found after MHT. Conclusion Continuous PbtO2 monitoring could be introduced to evaluate the condition of regional cerebral oxygen metabolism, thereby guiding the clinical treatment and predicting the outcome. PMID:27601907

  14. Sleep-wake cycling in a neonate admitted to the NICU: a video-EEG case study during hypothermia treatment.

    PubMed

    Axelin, Anna; Cilio, Maria Roberta; Asunis, Marilisa; Peloquin, Susan; Franck, Linda S

    2013-01-01

    This retrospective case study describes the sleep-wake cycles of an infant in the neonatal intensive care unit. We analyzed video-electroencephalographic recording of the term infant monitored during treatment with therapeutic hypothermia for hypoxic-ischemic encephalopathy. The continuous video-electroencephalographic recording over a 4-day period also allowed us to describe the following dimensions of daily care in relation to the infant's sleep-wake states: (1) handling by professional and parent caregivers and (2) stress, pain, and analgesia. Physical contact constituted 17% to 36% of each 24-hour period. The infant's care was fragmented, with a mean of 3 to 4 physical contacts per hour. As a result, the structure of infant sleep was altered by the increased amount of awake and quiet sleep. The number of painful procedures ranged from 5 to 24 per day. Nurses were the main care providers. Parents had more contact after the infant was rewarmed. This case study suggests that neonatal intensive care unit infants are exposed to frequent handling and stress as well as altered sleep. The cumulative negative impact of frequent handling and sleep fragmentation may go unnoticed by caregivers focused on episodes of care. Continuous video-electroencephalographic monitoring is a useful tool for longitudinal evaluation of infant sleep and responses to caregiving in the neonatal intensive care unit. PMID:23899806

  15. Life threatening central nervous system manifestations and hypothermia due to maneb intoxication in a child: a case report.

    PubMed

    de Tollenaer, S M; Buysse, Cmp; van den Anker, J N; Touw, D J; de Hoog, M

    2006-12-01

    Maneb, manganese ethylene-bis-dithiocarbamate, is a fungicide pesticide used in the agriculture and bulb flower culture sector. Toxicological effects for humans have been reported in literature and are diverse. They vary from allergic reactions (dermatitis, conjunctivitis, and bronchitis), central nervous system effects (muscarinic, nicotinic, central and extrapyramidal) and renal toxicity (acute renal failure).A 7-year old girl was admitted to the pediatric intensive care unit because of status epilepticus. Physical examination showed respiratory insufficiency, convulsions, and severe hypothermia (32.5 degrees C). The patient was intubated and her convulsions were successfully treated with benzodiazepines. Except for a combined metabolic and respiratory acidosis and hyperglycemia, diagnostic investigations on admission (full blood count, electrolytes, liver and renal functions, cerebrospinal fluid investigation, toxicology screening of blood and urine for barbiturates and benzodiazepines, blood culture, herpes PCR, and a CT scan of the brain) were normal. Within 24 hours, there was a complete recovery of all neurological signs. Within 72 hours, the patient was discharged from the hospital. Liquid chromatography-mass spectrometric investigation of her blood showed amounts of maneb, which can explain all symptoms and signs. However, effects of this magnitude on the central nervous system have not previously been reported in humans. PMID:17164699

  16. Relationship Between Cerebral Oxygenation and Metabolism During Rewarming in Newborn Infants After Therapeutic Hypothermia Following Hypoxic-Ischemic Brain Injury.

    PubMed

    Mitra, Subhabrata; Bale, Gemma; Meek, Judith; Uria-Avellanal, Cristina; Robertson, Nicola J; Tachtsidis, Ilias

    2016-01-01

    Therapeutic hypothermia (TH) has become a standard of care following hypoxic ischemic encephalopathy (HIE). After TH, body temperature is brought back to 37 °C over 14 h. Lactate/N-acetylasperatate (Lac/NAA) peak area ratio on proton magnetic resonance spectroscopy ((1)H MRS) is the best available outcome biomarker following HIE. We hypothesized that broadband near infrared spectroscopy (NIRS) measured changes in the oxidation state of cytochrome-c-oxidase concentration (Δ[oxCCO]) and cerebral hemodynamics during rewarming would relate to Lac/NAA. Broadband NIRS and systemic data were collected during rewarming from 14 infants following HIE over a mean period of 12.5 h. (1)H MRS was performed on day 5-9. Heart rate increased by 20/min during rewarming while blood pressure and peripheral oxygen saturation (SpO2) remained stable. The relationship between mitochondrial metabolism and oxygenation (measured as Δ[oxCCO] and Δ[HbD], respectively) was calculated by linear regression analysis. This was reviewed in three groups: Lac/NAA values <0.5, 0.5-1, >1. Mean regression coefficient (r (2)) values in these groups were 0.41 (±0.27), 0.22 (±0.21) and 0.01, respectively. The relationship between mitochondrial metabolism and oxygenation became impaired with rising Lac/NAA. Cardiovascular parameters remained stable during rewarming. PMID:27526150

  17. Galectin-3 expression in hippocampal CA2 following transient forebrain ischemia and its inhibition by hypothermia or antiapoptotic agents

    PubMed Central

    Hisamatsu, Kenji; Kobayashi, Kazuhiro; Miyazaki, Tatsuhiko; Hirata, Akihiro; Hatano, Yuichiro; Tomita, Hiroyuki; Hara, Akira

    2016-01-01

    Recent evidence has suggested that the hippocampal CA2 region plays an important role in the recognition process. We have reported that ischemic damage in the hippocampal CA2 region following transient ischemia is caused by apoptosis, but the underlying mechanisms are still not clear. Galectin-3 is a β-galactosidase-binding lectin that is important in cell proliferation and apoptotic regulation. We have also reported that galectin-3 was expressed in activated microglia in the CA1 region 96 h after transient ischemia. The aim of this study is to determine the localization and time course of galectin-3 expression in the CA2 region following transient forebrain ischemia. Galectin-3 immunostaining was observed in both interior side of CA1 region and CA2 region in hippocampus 60 h after ischemic insult. At 66 h, galectin-3 was observed in the whole CA1 region adjacent to the CA2 region in the hippocampus. Both galectin-3 expression and neuronal cell death in the CA2 region were significantly inhibited by hypothermia and by apoptosis-inhibiting reagents. These results suggest that galectin-3 in the CA2 region is expressed independent of that in the CA1 region. Protection of the expression of galectin-3 in the CA2 region might contribute toward the survival of CA2 pyramidal neurons. PMID:26848998

  18. Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial

    PubMed Central

    Azzopardi, Denis; Robertson, Nicola J; Bainbridge, Alan; Cady, Ernest; Charles-Edwards, Geoffrey; Deierl, Aniko; Fagiolo, Gianlorenzo; Franks, Nicholas P; Griffiths, James; Hajnal, Joseph; Juszczak, Edmund; Kapetanakis, Basil; Linsell, Louise; Maze, Mervyn; Omar, Omar; Strohm, Brenda; Tusor, Nora; Edwards, A David

    2016-01-01

    Summary Background Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. Methods Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK. Eligible infants were 36–43 weeks of gestational age, had signs of moderate to severe encephalopathy and moderately or severely abnormal background activity for at least 30 min or seizures as shown by amplitude-integrated EEG (aEEG), and had one of the following: Apgar score of 5 or less 10 min after birth, continued need for resuscitation 10 min after birth, or acidosis within 1 h of birth. Participants were allocated in a 1:1 ratio by use of a secure web-based computer-generated randomisation sequence within 12 h of birth to cooling to a rectal temperature of 33·5°C for 72 h (standard treatment) or to cooling in combination with 30% inhaled xenon for 24 h started immediately after randomisation. The primary outcomes were reduction in lactate to N-acetyl aspartate ratio in the thalamus and in preserved fractional anisotropy in the posterior limb of the internal capsule, measured with magnetic resonance spectroscopy and MRI, respectively, within 15 days of birth. The investigator assessing these outcomes was masked to allocation. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00934700, and with ISRCTN, as ISRCTN08886155. Findings The study was done from Jan 31, 2012, to Sept 30, 2014. We enrolled 92 infants, 46 of whom were randomly assigned to cooling only and 46 to xenon plus cooling. 37 infants in the cooling only group and 41 in the cooling plus xenon group underwent magnetic resonance assessments

  19. Amide proton signals as pH indicator for in vivo MRS and MRI of the brain-Responses to hypercapnia and hypothermia.

    PubMed

    Watanabe, Takashi; Frahm, Jens; Michaelis, Thomas

    2016-06-01

    Using proton MRS and MRI of mouse brain at 9.4T, this work provides the first in vivo evidence of pH-dependent concurrent changes of three amide signals and related metabolic responses to hypercapnia and hypothermia. During hypercapnia, amide proton MRS signals of glutamine at 6.8-6.9ppm and 7.6ppm as well as of unspecific compounds at 8.1-8.3ppm increase by at least 50% both at 37°C and 22°C. These changes reflect a reduced proton exchange with water. They are strongly correlated with intracellular pH which ranges from 6.75±0.10 to 7.13±0.06 as determined from a shift in creatine phosphokinase equilibrium. In MRI, saturation transfer from aliphatic as well as aromatic and/or amide protons alters slightly during hypercapnia and significantly during hypothermia. The asymmetry in magnetization transfer ratios decreased slightly during hypercapnia and hypothermia. Regardless of pH or temperature, saturation transfer from aliphatic protons between -2 and -4ppm frequency offset to water protons is significantly greater than that from aromatic/amide protons at corresponding offsets between +2 and +4ppm. Irradiation of aliphatic compounds at -3.5ppm frequency offset from water predominantly saturates lipids and water associated with myelin. Taken together, the results indicate that, for the B1 power used in this study, dipolar coupling between aliphatic and water protons rather than proton exchange is the dominant factor in Z-spectra and magnetization transfer ratio asymmetry of the brain in vivo. PMID:26975553

  20. Prevalence of troponin elevations in patients with cardiac arrest and implications for assessing quality of care in hypothermia centers.

    PubMed

    Kontos, Michael C; Ornato, Joseph P; Kurz, Michael C; Roberts, Charlotte S; Gossip, Michelle; Dhindsa, Harinder S; Reid, Renee D; Peberdy, Mary A

    2013-10-01

    The prevalence of troponin elevations in patients with cardiac arrest (CA) using newer generation troponin assays when the ninety-ninth percentile is used has not been well described. We studied patients admitted with CA without ST elevation myocardial infarction (MI). Treatment included a multidisciplinary protocol that included routine use of hypothermia for appropriate patients. Serial assessment of cardiac biomarkers, including troponin I was obtained over the initial 24 to 36 hours. Patients were classified into 1 of 5 groups on the basis of multiples of the ninety-ninth percentile (upper reference limit [URL]), using the peak troponin I value: <1×, 1 to 3×, 3 to 5×, 5 to 10×, and >10×. Serial changes between the initial and second troponin I values were also assessed. A total of 165 patients with CA (mean age 58 ± 16, 67% men) were included. Troponin I was detectable in all but 2 patients (99%); all others had peak troponin I values that were greater than or equal to the URL. Most patients had peak troponin I values >10× URL, including patients with ventricular fibrillation or ventricular tachycardia (85%), asystole (50%), and pulseless electrical activity (59%). Serial changes in troponin I were present in almost all patients: ≥20% change in 162 (98%), ≥30% change in 159 (96%), and an absolute increase of ≥0.02 ng/ml in 85% of patients. In conclusion, almost all patients with CA who survived to admission had detectable troponin I, most of whom met biomarker guideline criteria for MI. Given the high mortality of these patients, these data have important implications for MI mortality reporting at CA treatment centers. PMID:23800547

  1. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data

    PubMed Central

    Edwards, A David; Brocklehurst, Peter; Gunn, Alistair J; Halliday, Henry; Juszczak, Edmund; Levene, Malcolm; Strohm, Brenda; Thoresen, Marianne; Whitelaw, Andrew

    2010-01-01

    Objective To determine whether moderate hypothermia after hypoxic-ischaemic encephalopathy in neonates improves survival and neurological outcome at 18 months of age. Design A meta-analysis was performed using a fixed effect model. Risk ratios, risk difference, and number needed to treat, plus 95% confidence intervals, were measured. Data sources Studies were identified from the Cochrane central register of controlled trials, the Oxford database of perinatal trials, PubMed, previous reviews, and abstracts. Review methods Reports that compared whole body cooling or selective head cooling with normal care in neonates with hypoxic-ischaemic encephalopathy and that included data on death or disability and on specific neurological outcomes of interest to patients and clinicians were selected. Results We found three trials, encompassing 767 infants, that included information on death and major neurodevelopmental disability after at least 18 months’ follow-up. We also identified seven other trials with mortality information but no appropriate neurodevelopmental data. Therapeutic hypothermia significantly reduced the combined rate of death and severe disability in the three trials with 18 month outcomes (risk ratio 0.81, 95% confidence interval 0.71 to 0.93, P=0.002; risk difference −0.11, 95% CI −0.18 to −0.04), with a number needed to treat of nine (95% CI 5 to 25). Hypothermia increased survival with normal neurological function (risk ratio 1.53, 95% CI 1.22 to 1.93, P<0.001; risk difference 0.12, 95% CI 0.06 to 0.18), with a number needed to treat of eight (95% CI 5 to 17), and in survivors reduced the rates of severe disability (P=0.006), cerebral palsy (P=0.004), and mental and the psychomotor developmental index of less than 70 (P=0.01 and P=0.02, respectively). No significant interaction between severity of encephalopathy and treatment effect was detected. Mortality was significantly reduced when we assessed all 10 trials (1320 infants; relative risk 0

  2. Low doses of neurotensin in the preoptic area produce hyperthermia. Comparison with other brain sites and with neurotensin-induced analgesia.

    PubMed

    Benmoussa, M; Chait, A; Loric, G; de Beaurepaire, R

    1996-01-01

    High amounts of neurotensin (NT) are found in the preoptic area of the hypothalamus, an area known to be involved in the regulation of body temperature. It is generally believed that NT is a peptide that produces hypothermia, and several sites in the brain have been proposed to mediate NT-induced hypothermia, including the preoptic area. However, the doses of NT used in these experiments were always very high (microgram order) whereas, according to Goedert, the total brain content of NT in the rat does not exceed 10 ng. We therefore reinvestigated the effects of microinjections of NT in the brain, using high (5 micrograms) and low (50 and 5 ng) doses, into the preoptic area and other brain sites (cerebral ventricles, posterior hypothalamus, and nucleus accumbens), and we also studied, as a comparison, the effects of high and low doses of NT on pain sensitivity in the same sites. The results show that the preoptic area has unique properties in the regulation of body temperature: low doses of NT in the preoptic area produce a hyperthermic response, whereas high doses produce hypothermia. In comparison, NT produces hypothermia in the posterior hypothalamus whatever the dose, and NT has analgesic effects in the preoptic area only at high doses. Besides, NT has no thermic effect, but does have an analgesic effect, in the nucleus accumbens. The selectivity of the actions of high doses of NT, as well as the mechanism of action of NT (possibly an endogenous neuroleptic), are discussed. PMID:8705314

  3. Hypothermia inhibits cell proliferation and nitric oxide synthase expression in rats.

    PubMed

    Lee, Kwang-Sik; Lim, Baek-Vin; Jang, Mi-Hyeon; Shin, Min-Chul; Lee, Taeck-Hyun; Kim, Young-Pyo; Shin, Ho-Su; Cho, Seong-Yeon; Kim, Hong; Shin, Mal-Soon; Kim, Ee-Hwa; Kim, Chang-Ju

    2002-08-23

    In the present study, the effects of cold-water immersion on cell proliferation and nitric oxide synthase expression in the dentate gyrus of rats were investigated. Sprague-Dawley rats were divided into four groups: the control-rest group; the control-heat group; the cold-rest group; and the cold-heat group. Cold-water immersion for 5 min at 4 degrees C suppressed the numbers of 5-bromo-2'-deoxyuridine-positive and nicotinamide adenine dinucleotide phosphate-diaphorase-positive cells in the dentate gyrus, and these numbers were increased by warming for 30 min at 30 degrees C. In the present study, it was demonstrated that warming protects against cold stress-induced suppression of new cell formation, and results suggest that nitric oxide, the synthesis of which is affected adversely by cold-water immersion, may play an important role in the regulation of cell proliferation. PMID:12161261

  4. Why wrapping premature neonates to prevent hypothermia can predispose to overheating.

    PubMed

    Agourram, Bouchra; Bach, Véronique; Tourneux, Pierre; Krim, Gérard; Delanaud, Stéphane; Libert, Jean-Pierre

    2010-06-01

    Wrapping low-birth-weight neonates in a plastic bag prevents body heat loss. A bonnet can also be used, since large amounts of heat can be lost from the head region, but may provide too much thermal insulation, thus increasing the risk of overheating. We assessed the time required to reach warning body temperature (t38 degrees C), heat stroke (t40 degrees C), or extreme value (t43 degrees C) in a mathematical model that involved calculating various local body heat losses. Simulated heat exchanges were based on body surface temperature distribution measured in preterm neonates exposed to 33 degrees C air temperature (relative air humidity: 35%; air velocity: <0.1 m/s) and covered (torso and limbs) or not with a transparent plastic bag. We also compared metabolic heat production with body heat losses when a bonnet (2 or 3.5 mm thick) covered 10%, 40%, or 100% of the head. Wrapping neonates in a bag (combined or not with a bonnet) does not induce a critical situation as long as metabolic heat production does not increase. When endogenous heat production rises, t38 degrees C ranged between 75 and 287, t40 degrees C between 185 and 549, and t43 degrees C between 287 and 702 min. When this increase was accompanied by a fall in skin temperature, overheating risk was accentuated (37

  5. Lipid emulsion rapidly restores contractility in stunned mouse cardiomyocytes: A comparison with therapeutic hypothermia

    PubMed Central

    Li, Jing; Fettiplace, Michael; Sy-Jou, Chen; Steinhorn, Benjamin; Shao, Zuohui; Zhu, Xiangdong; Li, Changqing; Harty, Shaun; Weinberg, Guy; Vanden Hoek, Terry L.

    2014-01-01

    Objective Cooling following cardiac arrest can improve survival significantly. However, delays in achieving target temperature may decrease the overall benefits of cooling. Here we test whether lipid emulsion, a clinically approved drug reported to exert cardioprotection, can rescue heart contractility in the setting of delayed cooling in stunned mouse cardiomyocytes. Design Cell culture study Setting Academic research laboratory Subjects Cardiomyocytes isolated from 1–2-day old C57BL6 mice Interventions Cardiomyocytes were exposed to 30 minutes of ischemia followed by 90 minutes reperfusion and 10 minutes isoproterenol with nine interventions: 1) no additional treatment; 2) intra-ischemic cooling at 32°C initiated 10 min prior to reperfusion; 3) delayed cooling started 20 minutes after reperfusion; 4) lipid emulsion + delayed cooling; 5) lipid emulsion (0.25%) administered at reperfusion; 6) lipid emulsion + intra-ischemic cooling; 7) delayed lipid emulsion; 8) lipid emulsion + delayed cooling + Akt inhibitor (API-2, 10 μM) and 9) lipid emulsion + delayed cooling + Erk inhibitor (U0126, 10 μM). Inhibitors were given to cells 1 h prior to ischemia. Measurements and Main Results Contractility was recorded by real-time phase-contrast imaging and analyzed with pulse image velocimetry in MATLAB. Ischemia diminished cell contraction. The cardioprotective effect of cooling was diminished when delayed but was rescued by lipid emulsion. Further, lipid emulsion on its own improved recovery of the contractility to an equal extent as intra-ischemic cooling. However, co-treatment of lipid emulsion and intra-ischemic cooling did not further improve the recovery compared to either treatment alone. Moreover, Akt and Erk inhibitors blocked lipid emulsion-induced protection. Conclusion Lipid emulsion improved contractility and rescued contractility in the context of delayed cooling. This protective effect required Akt and Erk signaling. Lipid emulsion might serve as a

  6. Electroencephalogram and Magnetic Resonance Imaging Comparison as a Predicting Factor for Neurodevelopmental Outcome in Hypoxic Ischemic Encephalopathy Infant Treated with Hypothermia

    PubMed Central

    Del Balzo, Francesca; Maiolo, Stella; Papoff, Paola; Giannini, Luigi; Moretti, Corrado; Properzi, Enrico; Spalice, Alberto

    2014-01-01

    Hypoxic-ischemic encephalopathy (HIE) is an important cause of acute neurological damage in newborns at (or near) term. Several trials in recent years have shown that moderate hypothermia by total body cooling or selective head is an effective intervention to reduce mortality and major disability in infants survived a perinatal hypoxic-ischemic attack. Follow-up in these patients is very important to establish neurodevelopmental outcome, and specific markers can lead us to detect predicting sign for good or poor outcome. We reported a few cases of newborn with HIE treated with hypothermia, in whom the comparison between electroencephalogram (EEG) and magnetic resonance imaging (MRI) represents the first marker for neurodevelopment outcome prediction. The continuous EEG monitoring showed a depressed EEG activity with diffuse burst depression in 7 patients. No epileptic abnormalities were registered. In 10 out of 20 patients no abnormalities of the background activity and no epileptic abnormalities were observed. We found that a depressed EEG activity during the first 72 h of life and a diffused alteration of basal ganglia at MRI were correlated with a poor neurodevelopmental outcome at 18 months of follow-up. PMID:25635216

  7. Preoperative forced-air warming combined with intraoperative warming versus intraoperative warming alone in the prevention of hypothermia during gynecologic surgery.

    PubMed

    Adriani, Melissa Bucci; Moriber, Nancy

    2013-12-01

    Hypothermia in the perioperative setting can have serious consequences, including increased risk of infection or adverse cardiac events. Forced-air warming units commonly are used to prevent hypothermia. This study examined the impact of adding preoperative warming (Bair Paws, 3M) to conventional intraoperative forced-air warming modalities. Thirty patients received both preoperative and intraoperative forced-air warming, and 30 patients received intraoperative warming alone. Temperature readings were recorded across 3 time periods: preoperative, intraoperative, and postoperative. Data were analyzed using descriptive statistics, analysis of variance (ANOVA), and repeated-measures ANOVA. Demographics were similar in both groups with respect to age, body mass index, total intravenous fluids, and estimated blood loss. Statistically significant differences in temperature were seen over time (df = 2, P < .001), and for each intervention across all 3 time periods (P = .042). However, no statistically significant differences in temperature were demonstrated between groups over time. ASA status and type of procedure (laparoscopic vs open) also had no impact on results. These results suggest that preoperative warming with the Bair Paws gown offers no benefit over conventional therapy in maintaining normothermia in the perioperative period. PMID:24597006

  8. Electroencephalogram and magnetic resonance imaging comparison as a predicting factor for neurodevelopmental outcome in hypoxic ischemic encephalopathy infant treated with hypothermia.

    PubMed

    Del Balzo, Francesca; Maiolo, Stella; Papoff, Paola; Giannini, Luigi; Moretti, Corrado; Properzi, Enrico; Spalice, Alberto

    2014-08-12

    Hypoxic-ischemic encephalopathy (HIE) is an important cause of acute neurological damage in newborns at (or near) term. Several trials in recent years have shown that moderate hypothermia by total body cooling or selective head is an effective intervention to reduce mortality and major disability in infants survived a perinatal hypoxic-ischemic attack. Follow-up in these patients is very important to establish neurodevelopmental outcome, and specific markers can lead us to detect predicting sign for good or poor outcome. We reported a few cases of newborn with HIE treated with hypothermia, in whom the comparison between electroencephalogram (EEG) and magnetic resonance imaging (MRI) represents the first marker for neurodevelopment outcome prediction. The continuous EEG monitoring showed a depressed EEG activity with diffuse burst depression in 7 patients. No epileptic abnormalities were registered. In 10 out of 20 patients no abnormalities of the background activity and no epileptic abnormalities were observed. We found that a depressed EEG activity during the first 72 h of life and a diffused alteration of basal ganglia at MRI were correlated with a poor neurodevelopmental outcome at 18 months of follow-up. PMID:25635216

  9. The TOBY Study. Whole body hypothermia for the treatment of perinatal asphyxial encephalopathy: A randomised controlled trial

    PubMed Central

    Azzopardi, Dennis; Brocklehurst, Peter; Edwards, David; Halliday, Henry; Levene, Malcolm; Thoresen, Marianne; Whitelaw, Andrew

    2008-01-01

    Background A hypoxic-ischaemic insult occurring around the time of birth may result in an encephalopathic state characterised by the need for resuscitation at birth, neurological depression, seizures and electroencephalographic abnormalities. There is an increasing risk of death or neurodevelopmental abnormalities with more severe encephalopathy. Current management consists of maintaining physiological parameters within the normal range and treating seizures with anticonvulsants. Studies in adult and newborn animals have shown that a reduction of body temperature of 3–4°C after cerebral insults is associated with improved histological and behavioural outcome. Pilot studies in infants with encephalopathy of head cooling combined with mild whole body hypothermia and of moderate whole body cooling to 33.5°C have been reported. No complications were noted but the group sizes were too small to evaluate benefit. Methods/Design TOBY is a multi-centre, prospective, randomised study of term infants after perinatal asphyxia comparing those allocated to "intensive care plus total body cooling for 72 hours" with those allocated to "intensive care without cooling". Full-term infants will be randomised within 6 hours of birth to either a control group with the rectal temperature kept at 37 +/- 0.2°C or to whole body cooling, with rectal temperature kept at 33–34°C for 72 hours. Term infants showing signs of moderate or severe encephalopathy +/- seizures have their eligibility confirmed by cerebral function monitoring. Outcomes will be assessed at 18 months of age using neurological and neurodevelopmental testing methods. Sample size At least 236 infants would be needed to demonstrate a 30% reduction in the relative risk of mortality or serious disability at 18 months. Recruitment was ahead of target by seven months and approvals were obtained allowing recruitment to continue to the end of the planned recruitment phase. 325 infants were recruited. Primary outcome Combined

  10. Avoidance of Profound Hypothermia During Initial Reperfusion Improves the Functional Recovery of Hearts Donated After Circulatory Death.

    PubMed

    White, C W; Ambrose, E; Müller, A; Li, Y; Le, H; Thliveris, J; Arora, R C; Lee, T W; Dixon, I M C; Tian, G; Nagendran, J; Hryshko, L V; Freed, D H

    2016-03-01

    The resuscitation of hearts donated after circulatory death (DCD) is gaining widespread interest; however, the method of initial reperfusion (IR) that optimizes functional recovery has not been elucidated. We sought to determine the impact of IR temperature on the recovery of myocardial function during ex vivo heart perfusion (EVHP). Eighteen pigs were anesthetized, mechanical ventilation was discontinued, and cardiac arrest ensued. A 15-min standoff period was observed and then hearts were reperfused for 3 min at three different temperatures (5°C; N = 6, 25°C; N = 5, and 35°C; N = 7) with a normokalemic adenosine-lidocaine crystalloid cardioplegia. Hearts then underwent normothermic EVHP for 6 h during which time myocardial function was assessed in a working mode. We found that IR coronary blood flow differed among treatment groups (5°C = 483 ± 53, 25°C = 722 ± 60, 35°C = 906 ± 36 mL/min, p < 0.01). During subsequent EVHP, less myocardial injury (troponin I: 5°C = 91 ± 6, 25°C = 64 ± 16, 35°C = 57 ± 7 pg/mL/g, p = 0.04) and greater preservation of endothelial cell integrity (electron microscopy injury score: 5°C = 3.2 ± 0.5, 25°C = 1.8 ± 0.2, 35°C = 1.7 ± 0.3, p = 0.01) were evident in hearts initially reperfused at warmer temperatures. IR under profoundly hypothermic conditions impaired the recovery of myocardial function (cardiac index: 5°C = 3.9 ± 0.8, 25°C = 6.2 ± 0.4, 35°C = 6.5 ± 0.6 mL/minute/g, p = 0.03) during EVHP. We conclude that the avoidance of profound hypothermia during IR minimizes injury and improves the functional recovery of DCD hearts. PMID:26780159

  11. Cholera toxin effects on body temperature changes induced by morphine.

    PubMed

    Basilico, L; Parenti, M; Fumagalli, A; Parolaro, D; Giagnoni, G

    1997-03-01

    The present study evaluates the influence of cholera toxin and its B-subunit on thermic responses to morphine in the rats. The holotoxin (1 microg/rat) and the B-subunit (5 microg) were administered ICV and three days later rats were challenged ICV with morphine and tested for changes of body temperature. Cholera toxin, but not its B-subunit, modified the time course of the hyperthermic response induced by a low dose of morphine (2.5 microg), converted the hypothermia due to a higher dose of morphine (18 microg) to a consistent hyperthermia and only partially reduced the greater hypothermia induced by 36 microg of morphine. Cholera toxin-induced modifications of thermic responses to morphine were paralleled with a decreased Gs(alpha) immunoreactivity and a reduced ability for the toxin to catalyse the "in vitro" ADP-ribosylation of Gs(alpha) in hypothalamic membranes. In contrast, at the same time when morphine-induced effects on body temperature were assessed, no changes in pertussis toxin-mediated ADP-ribosylation of Gi(alpha)/Go(alpha), or basal adenylate cyclase activity, or binding of mu-opioid receptor selective ligand [3H]-DAMGO were observed in hypothalamic areas from rats treated with cholera toxin. These findings suggest that adaptative events secondary to prolonged activation of Gs(alpha) play a role in the modifications of thermic responses to morphine induced by CTX. PMID:9077589

  12. Acute effects of a parkinsonism-inducing neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on mouse body temperature.

    PubMed

    Satoh, N; Yonezawa, A; Tadano, T; Kisara, K; Arai, Y; Kinemuchi, H

    1987-09-14

    The parkinsonism-inducing neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) given in single systemic doses (i.p.) to mice produced marked hyperthermia, and subsequent long-lasting hypothermia. Administration of MPTP or its oxidized product, 1-methyl-4-phenylpyridinium ion, MPP+, via i.c.v. resulted in only hypothermia. In contrast, i.p. MPP+ administration resulted in only hyperthermia. The MPTP-induced hyperthermia (i.p.) was blocked by quaternary derivatives of anti-cholinergic agents, atropine and scopolamine, but not by the tertiary-derivative of atropine. Duration of this hyperthermic effect was potentiated by neostigmine. Pretreatment with 1-deprenyl did not prevent hypothermia, but nomifensine partially or clorgyline completely prevented the effect without preventing MPTP-induced hyperthermia. The thermic effects by MPTP, unlike its neurotoxicity for the nigrostriatal DA system, may not require metabolism to MPP+. These results indicate that peripheral cholinergic functions are responsible for the MPTP-induced hyperthermia, whereas its hypothermic effect may be centrally mediated via dysregulation of the various neuron systems. PMID:3498107

  13. Efficacy and Safety of Plastic Wrap for Prevention of Hypothermia after Birth and during NICU in Preterm Infants: A Systematic Review and Meta-Analysis

    PubMed Central

    Li, Shaojun; Guo, Pengfei; Zou, Qing; He, Fuxiang; Xu, Feng; Tan, Liping

    2016-01-01

    Objective This meta-analysis aimed to investigate the efficacy and safety of plastic wrap applied after birth and during NICU in preterm infants for prevention of heat loss in preterm infants. Study Methods The Medline (1950 to August 2015), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7, 2015), CINAHL (1982 to August 2015) and the Embase (1974 to August 2015) databases were searched for randomized controlled trials (RCTs) or quasi-RCTs with main outcomes related to the core temperature (baseline temperature and/or post-stabilization temperature), hypothermia, mortality rate and hyperthermia. Result The included studies were of low to moderate quality. Compared with unwrapped infants, plastic wrap was associated with a significantly higher baseline temperature and post-stabilization temperature both in infants < 28 weeks of gestation (mean difference [MD] = 0.62, 95% CI 0.38 to 0.85; MD = 0.41, 95% CI 0.33 to 0.50, respectively), and in infants between 28 to 34 weeks of gestation (MD = 0.54, 95% CI 0.21 to 0.87; MD = 0.64, 95% CI 0.45 to 0.82, respectively). Use of plastic wrap was associated with lower incidence of hypothermia (relative risk [RR] = 0.70, 95% CI 0.63 to 0.78). However, use of plastic wrap in preterm infants was not associated with decrease in mortality (RR: 0.88, 95% CI 0.70 to 1.12, P = 0.31). Incidence of hyperthermia was significantly higher in the plastic wrap group as compared to that in the control group (RR = 2.55, 95% CI: 1.56 to 4.15, P = 0.0002). Hyperthermia in the plastic wrap group was resolved within one or two hours after unwrapping the babies. Conclusion Plastic wrap can be considered an effective and safe additional intervention to prevent hypothermia in preterm infants. However, its cost-effectiveness and long-term effect on mortality needs to be ascertained by conducting well-designed studies with longer follow-up period. PMID:27281027

  14. Endoplasmic Reticulum-Associated rht-PA Processing in CHO Cells: Influence of Mild Hypothermia and Specific Growth Rates in Batch and Chemostat Cultures

    PubMed Central

    Vergara, Mauricio; Berrios, Julio; Martínez, Irene; Díaz-Barrera, Alvaro; Acevedo, Cristian; Reyes, Juan G.; Gonzalez, Ramon; Altamirano, Claudia

    2015-01-01

    Background Chinese hamster ovary (CHO) cells are the main host for producing recombinant proteins with human therapeutic applications mainly because of their capability to perform proper folding and glycosylation processes. In addition, mild hypothermia is one of the main strategies for maximising the productivity of these systems. However, little information is available on the effect of culture temperature on the folding and degradation processes of recombinant proteins that takes place in the endoplasmic reticulum. Methods In order to evaluate the effect of the mild hypothermia on processing/endoplasmatic reticulum-associated degradation (ERAD) processes, batch cultures of CHO cells producing recombinant human tissue plasminogen activator (rht-PA) were carried out at two temperatures (37°C and 33°C) and treated with specific inhibitors of glycosylation and ERAD I (Ubiquitin/Proteasome system) or ERAD II (Autophagosoma/Lisosomal system) pathways. The effect of mild hypothermia was analysed separately from its indirect effect on specific cell growth rate. To do this, chemostat cultures were carried out at the same incubation conditions as the batch cultures, controlling cell growth at high (0.017 h-1) and low (0.012 h-1) dilution rates. For a better understanding of the investigated phenomenon, cell behaviour was also analysed using principal component analysis (PCA). Results and Conclusion Results suggest that rht-PA is susceptible to degradation by both ERAD pathways studied, revealing that processing and/or ERAD processes are sensitive to temperature cultivation in batch culture. Moreover, by isolating the effect of culture temperature from the effect of cell growth rate verifyed by using chemostat cultures, we have found that processing and/or ERAD processes are more sensitive to reduction in specific growth rate than low temperature, and that temperature reduction may have a positive effect on protein processing. Interestingly, PCA indicated that the

  15. Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy

    PubMed Central

    Shankaran, Seetha; McDonald, Scott A.; Laptook, Abbot R.; Hintz, Susan R.; Barnes, Patrick D.; Das, Abhik; Pappas, Athina; Higgins, Rosemary D.

    2015-01-01

    Objective To examine the ability of magnetic resonance imaging (MRI) patterns of neonatal brain injury defined by the National Institute of Child Health and Human Development Neonatal Research Network to predict death or IQ at 6–7 years of age following hypothermia for neonatal encephalopathy. Study design Out of 208 participants, 124 had MRI and primary outcome (death or IQ <70) data. The relationship between injury pattern and outcome was assessed. Results Death or IQ <70 occurred in 4 of 50 (8%) of children with pattern 0 (normal MRI), 1 of 6 (17%) with 1A (minimal cerebral lesions), 1 of 4 (25%) with 1B (extensive cerebral lesions), 3 of 8 (38%) with 2A (basal ganglia thalamic, anterior or posterior limb of internal capsule, or watershed infarction), 32 of 49 (65%) with 2B (2A with cerebral lesions), and 7 of 7 (100%) with pattern 3 (hemispheric devastation), P < .001; this association was also seen within hypothermia and control subgroups. IQ was 90 ± 13 among the 46 children with a normal MRI and 69 ± 25 among the 50 children with an abnormal MRI. In childhood, for a normal outcome, a normal neonatal MRI had a sensitivity of 61%, specificity of 92%, a positive predictive value of 92%, and a negative predictive value of 59%; for death or IQ <70, the 2B and 3 pattern combined had a sensitivity of 81%, specificity of 78%, positive predictive value of 70%, and a negative predictive value of 87%. Conclusions The Neonatal Research Network MRI pattern of neonatal brain injury is a biomarker of neurodevelopmental outcome at 6–7 years of age. PMID:26387012

  16. Fever Control Management Is Preferable to Mild Therapeutic Hypothermia in Traumatic Brain Injury Patients with Abbreviated Injury Scale 3-4: A Multi-Center, Randomized Controlled Trial.

    PubMed

    Hifumi, Toru; Kuroda, Yasuhiro; Kawakita, Kenya; Yamashita, Susumu; Oda, Yasutaka; Dohi, Kenji; Maekawa, Tsuyoshi

    2016-06-01

    In our prospective, multi-center, randomized controlled trial (RCT)-the Brain Hypothermia (B-HYPO) study-we could not show any difference on neurological outcomes in patients probably because of the heterogeneity in the severity of their traumatic condition. We therefore aimed to clarify and compare the effectiveness of the two therapeutic temperature management regimens in severe (Abbreviated Injury Scale [AIS] 3-4) or critical trauma patients (AIS 5). In the present post hoc B-HYPO study, we re-evaluated data based on the severity of trauma as AIS 3-4 or AIS 5 and compared Glasgow Outcome Scale score and mortality at 6 months by per-protocol analyses. Consequently, 135 patients were enrolled. Finally, 129 patients, that is, 47 and 31 patients with AIS 3-4 and 36 and 15 patients with AIS 5 were allocated to the mild therapeutic hypothermia (MTH) and fever control groups, respectively. No significant intergroup differences were observed with regard to age, gender, scores on head computed tomography (CT) scans, and surgical operation for traumatic brain injury (TBI), except for Injury Severity Score (ISS) in AIS 5. The fever control group demonstrated a significant reduction of TBI-related mortality compared with the MTH group (9.7% vs. 34.0%, p = 0.02) and an increase of favorable neurological outcomes (64.5% vs. 51.1%, p = 0.26) in patients with AIS 3-4, although the latter was not statistically significant. There was no difference in mortality or favorable outcome in patients with AIS 5. Fever control may be considered instead of MTH in patients with TBI (AIS 3-4). PMID:26413933

  17. Alterations in Blood-Brain Barrier Permeability to Large and Small Molecules and Leukocyte Accumulation after Traumatic Brain Injury: Effects of Post-Traumatic Hypothermia

    PubMed Central

    Lotocki, George; de Rivero Vaccari, Juan Pablo; Perez, Enrique R.; Sanchez-Molano, Juliana; Furones-Alonso, Ofelia; Bramlett, Helen M.

    2009-01-01

    Abstract We investigated the temporal and regional profile of blood-brain barrier (BBB) permeability to both large and small molecules after moderate fluid percussion (FP) brain injury in rats and determined the effects of post-traumatic modest hypothermia (33°C/4 h) on these vascular perturbations. The visible tracers biotin-dextrin-amine 3000 (BDA-3K, 3 kDa) and horseradish peroxidase (HRP, 44 kDa) were injected intravenously at 4 h or 3 or 7 days post-TBI. At 30 min after the tracer infusion, both small and large molecular weight tracers were detected in the contusion area as well as remote regions adjacent to the injury epicenter in both cortical and hippocampal structures. In areas adjacent to the contusion site, increased permeability to the small molecular weight tracer (BDA-3K) was evident at 4 h post-TBI and remained visible after 7 days survival. In contrast, the larger tracer molecule (HRP) appeared in these remote areas at acute permeable sites but was not detected at later post-traumatic time periods. A regionally specific relationship was documented at 3 days between the late-occurring permeability changes observed with BDA-3K and the accumulation of CD68-positive macrophages. Mild hypothermia initiated 30 min after TBI reduced permeability to both large and small tracers and the infiltration of CD68-positive cells. These results indicate that moderate brain injury produces temperature-sensitive acute, as well as more long-lasting vascular perturbations associated with secondary injury mechanisms. PMID:19558276

  18. Factors influencing survival of mammalian cells exposed to hypothermia. V. Effects of hepes, free radicals, and H sub 2 O sub 2 under light and dark conditions

    SciTech Connect

    Zieger, M.A.; Glofcheski, D.J.; Lepock, J.R.; Kruuv, J. )

    1991-02-01

    Cytotoxicity resulting from the interaction of fluorescent light from a flow hood with Hepes-buffered cell culture medium at room temperature was demonstrated. Toxicity was prevented by keeping both cells (V79 Chinese hamster) and medium shielded from direct fluorescent light ('dark conditions') or by supplementing the medium with 10 micrograms/ml catalase; this suggests that extracellular hydrogen peroxide is a major cause of the lethal effect under 'lighted conditions.' No sensitization resulted from the exposure of cells in a sodium bicarbonate (SBC)-buffered medium to fluorescent light, nor in a catalase supplemented SBC-buffered medium. The Hepes/light reaction during routine cell manipulations presensitized cells to hypothermia damage in the dark with the presensitization being more severe for 5 than for 10 degrees C hypothermic exposure. Presensitization was prevented by performing the complete experiment under dark conditions or by supplementing the medium with 10 micrograms/ml catalase. However, catalase did not improve the hypothermic survival when experiments were performed under dark conditions. Hence, 10 micrograms/ml catalase does not protect cells from hypothermic (5 and 10 degrees C) damage per se, but rather from Hepes/light sublethal damage which interacts with hypothermic sublethal damage to result in lethal lesions. Additionally, under dark conditions, superoxide dismutase (SOD), allopurinol, catalase plus SOD, DMSO, or mannitol did not improve survival when present during hypothermic storage, suggesting that extracellular superoxide anion, hydrogen peroxide, or hydroxyl radicals are not the cause of cell killing under conditions of pure hypothermia uncomplicated by prehypothermic ischemia or hypoxia.

  19. Near-Infrared Spectroscopy versus Magnetic Resonance Imaging To Study Brain Perfusion in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

    PubMed Central

    Wintermark, P.; Hansen, A.; Warfield, SK.; Dukhovny, D.; Soul, JS.

    2014-01-01

    Background The measurement of brain perfusion may provide valuable information for assessment and treatment of newborns with hypoxic-ischemic encephalopathy (HIE). While arterial spin labeled perfusion (ASL) magnetic resonance imaging (MRI) provides noninvasive and direct measurements of regional cerebral blood flow (CBF) values, it is logistically challenging to obtain. Near-infrared spectroscopy (NIRS) might be an alternative, as it permits noninvasive and continuous monitoring of cerebral hemodynamics and oxygenation at the bedside. Objective The purpose of this study is to determine the correlation between measurements of brain perfusion by NIRS and by MRI in term newborns with HIE treated with hypothermia. Design/Methods In this prospective cohort study, ASL-MRI and NIRS performed during hypothermia were used to assess brain perfusion in these newborns. Regional cerebral blood flow values (CBF), measured from 1–2 MRI scans for each patient, were compared to mixed venous saturation values (SctO2) recorded by NIRS just before and after each MRI. Analysis included groupings into moderate versus severe HIE based on their initial background pattern of amplitude-integrated electroencephalogram. Results Twelve concomitant recordings were obtained of seven neonates. Strong correlation was found between SctO2 and CBF in asphyxiated newborns with severe HIE (r = 0.88; p value = 0.0085). Moreover, newborns with severe HIE had lower CBF (likely lower oxygen supply) and extracted less oxygen (likely lower oxygen demand or utilization) when comparing SctO2 and CBF to those with moderate HIE. Conclusions NIRS is an effective bedside tool to monitor and understand brain perfusion changes in term asphyxiated newborns, which in conjunction with precise measurements of CBF obtained by MRI at particular times, may help tailor neuroprotective strategies in term newborns with HIE. PMID:23631990

  20. Mild therapeutic hypothermia is superior to controlled normothermia for the maintenance of blood pressure and cerebral oxygenation, prevention of organ damage and suppression of oxidative stress after cardiac arrest in a porcine model

    PubMed Central

    2013-01-01

    Background Mild therapeutic hypothermia (HT) has been implemented in the management of post cardiac arrest (CA) syndrome after the publication of clinical trials comparing HT with common practice (ie, usually hyperthermia). Current evidence on the comparison between therapeutic HT and controlled normothermia (NT) in CA survivors, however, remains insufficient. Methods Eight female swine (sus scrofa domestica; body weight 45 kg) were randomly assigned to receive either mild therapeutic HT or controlled NT, with four animals per group. Veno-arterial extracorporeal membrane oxygenation (ECMO) was established and at minimal ECMO flow (0.5 L/min) ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of CA, circulation was restored by increasing the ECMO flow to 4.5 L/min; 90 min of reperfusion followed. Target core temperatures (HT: 33°C; NT: 36.8°C) were maintained using the heat exchanger on the oxygenator. Invasive blood pressure was measured in the aortic arch, and cerebral oxygenation was assessed using near-infrared spectroscopy. After 60 min of reperfusion, up to three defibrillation attempts were performed. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I (TnI), myoglobin (MGB), creatine-phosphokinase (CPK), alanin-aminotransferase (ALT), neuron-specific enolase (NSE) and cystatin C (CysC) levels. Reactive oxygen metabolite (ROM) levels and biological antioxidant potential (BAP) were also measured. Results Significantly higher blood pressure and cerebral oxygenation values were observed in the HT group (P<0.05). Sinus rhythm was restored in all of the HT animals and in one from the NT group. The levels of TnI, MGB, CPK, ALT, and ROM were significantly lower in the HT group (P<0.05); levels of NSE, CysC, and BAP were comparable in both groups. Conclusions Our results from animal model of cardiac arrest indicate that HT may be superior to NT for the maintenance of blood pressure, cerebral

  1. Better lactate clearance associated with good neurologic outcome in survivors who treated with therapeutic hypothermia after out-of-hospital cardiac arrest

    PubMed Central

    2013-01-01

    Introduction Several methods have been proposed to evaluate neurological outcome in out-of-hospital cardiac arrest (OHCA) patients. Blood lactate has been recognized as a reliable prognostic marker for trauma, sepsis, or cardiac arrest. The objective of this study was to examine the association between initial lactate level or lactate clearance and neurologic outcome in OHCA survivors who were treated with therapeutic hypothermia. Methods This retrospective cohort study included patients who underwent protocol-based 24-hour therapeutic hypothermia after OHCA between January 2010 and March 2012. Serum lactate levels were measured at the start of therapy (0 hours), and after 6 hours, 12 hours, 24 hours, 48 hours and 72 hours. The 6 hour and 12 hour lactate clearance were calculated afterwards. Patients’ neurologic outcome was assessed at one month after cardiac arrest; good neurological outcome was defined as Cerebral Performance Category one or two. The primary outcome was an association between initial lactate level and good neurologic outcome. The secondary outcome was an association between lactate clearance and good neurologic outcome in patients with initial lactate level >2.5 mmol/l. Results Out of the 76 patients enrolled, 34 (44.7%) had a good neurologic outcome. The initial lactate level showed no significant difference between good and poor neurologic outcome groups (6.07 ±4 .09 mmol/L vs 7.13 ± 3.99 mmol/L, P = 0.42), However, lactate levels at 6 hours, 12 hours, 24 hours, and 48 hours in the good neurologic outcome group were lower than in the poor neurologic outcome group (3.81 ± 2.81 vs 6.00 ± 3.22 P <0.01, 2.95 ± 2.07 vs 5.00 ± 3.49 P <0.01, 2.17 ± 1.24 vs 3.86 ± 3.92 P <0.01, 1.57 ± 1.02 vs 2.21 ± 1.35 P = 0.03, respectively). The secondary analysis showed that the 6-hour and 12-hour lactate clearance was higher for good neurologic outcome patients (35.3 ± 34.6% vs 6.89

  2. The effects of the β1 antagonist, metoprolol, on methamphetamine-induced changes in core temperature in the rat.

    PubMed

    Harrell, Ricki; Speaker, H Anton; Mitchell, Scott L; Sabol, Karen E

    2015-11-16

    Methamphetamine (METH) results in hyperthermia or hypothermia depending on environmental conditions. Here we studied the role of the β1 adrenergic receptor in mediating METH's temperature effects. Core temperature measurements were made telemetrically over a 7.5h session, two days/week, in test chambers regulated at either 18°C, 24°C, or 30°C ambient temperature. Rats were treated with the β1 antagonist metoprolol (5.0, 10.0, and 15.0mg/kg) alone (Experiment 1), or in combination with 5.0mg/kg METH (Experiment 2). In experiment 3, we combined a lower dose range of metoprolol (0.75, 1.5, and 3.0mg/kg) with 5.0mg/kg METH at 18°C and 30°C. Confirming prior findings, METH alone resulted in hyperthermia in warm (30°) and hypothermia in cool environments (18°C). Metoprolol alone induced small but significant increases in core temperature. In combination, however, metoprolol reduced METH-induced changes in core temperature. Specifically, at 30°C, 3.0, 5.0, 10.0, and 15.0mg/kg metoprolol decreased METH-induced hyperthermia; at 18°C, all six doses of metoprolol enhanced METH-induced hypothermia. Our metoprolol findings suggest that one component of METH's temperature effects involves increasing core temperature at all ambient conditions via β1 receptors. Since β receptors are involved in brown adipose tissue (BAT)-mediated thermogenesis, skeletal muscle-mediated thermogenesis, heart rate, and the metabolism of glucose and lipids, we discuss each of these as possible mechanisms for metoprolol's effects on METH-induced changes in core temperature. PMID:26388403

  3. Transfontanellar Duplex Brain Ultrasonography Resistive Indices as a Prognostic Tool in Neonatal Hypoxic-Ischemic Encephalopathy Before and After Treatment with Therapeutic Hypothermia

    PubMed Central

    Gerner, Gwendolyn J; Burton, V Joanna; Poretti, Andrea; Bosemani, Thangamadhan; Cristofalo, Elizabeth; Tekes, Aylin; Seyfert, Donna; Parkinson, Charlamaine; Leppert, Mary; Allen, Marilee; Huisman, Thierry A G M; Northington, Frances J; Johnston, Michael V

    2015-01-01

    OBJECTIVE Prior to therapeutic hypothermia (i.e., cooling), transfontanellar duplex brain sonography resistive indices (RI) were studied as bedside non-invasive measures of cerebral hemodynamics in neonates who suffered from hypoxic-ischemic encephalopathy (HIE). We compared pre- and post-cooling RI values and examined the relationships between RI values and specific long-term neurodevelopmental outcomes. STUDY DESIGN Transfontanellar duplex brain sonography, including RI, were obtained for 28 neonates prior to brain cooling and for 20 neonates following brain cooling. All RI values were sampled in the anterior cerebral artery at the beginning of each ultrasound study. Neurodevelopmental assessment was conducted between ages 20-32 months with the Mullen Scale of Early Learning. The relationships between pre- and post-cooling RI and cognitive and motor outcomes were studied. RESULT Neonates with RI values <0.60 prior to and following cooling were more likely to die or have severe neurodevelopmental disability by ages 20-32 months than those with RI >0.60. Lower RI values were associated with specific neurodevelopmental deficits in motor skill attainment. CONCLUSION Pre- and post-cooling transfontanellar duplex brain sonography RI values may be a useful prognostic tool, in conjunction with other clinical information, for neonates diagnosed with HIE. The results of this study suggest that further study of the prognostic value of RI values for short- and long-term outcomes is warranted. PMID:26609871

  4. Passive Warming using a Heat-Band versus a Resistive Heating Blanket for the Prevention of Inadvertent Perioperative Hypothermia during Laparotomy for Gynaecological Surgery

    PubMed Central

    Wan Fadzlina, Wan Muhd Shukeri; Wan Mohd Nazaruddin, Wan Hassan; Rhendra Hardy, Mohamad Zaini

    2016-01-01

    Background Inadvertent perioperative hypothermia (IPH) is a common problem, despite advancements in a variety of warming systems. The use of a resistive heating blanket (RHB) is a common but costly approach to patient warming. We have introduced the use of a heat-band in our centre as a cost-effective alternative to the RHB for patient warming. The efficacy of the heat-band in preventing IPH during laparotomy for gynaecological surgeries was compared with that of the RHB. Methods Thirty-two patients undergoing surgeries under combined general-epidural anaesthesia, with an expected duration of surgery of 2–4 h, were randomised to receive either the heat-band or RHB. The core body temperatures of the two groups were compared at several perioperative times, in addition to the incidence of post-anaesthesia shivering, time to extubation and intraoperative blood loss. Results The core body temperatures were comparable between the two groups in the pre-operative period, immediately after the induction of anaesthesia and skin incision, 1 h after the incision, at the time of complete skin closing, at extubation, upon arrival to the recovery room and 1 h post-operatively. There were no significant between-group differences in the incidence of post-anaesthesia shivering, time to extubation and intra-operative blood loss. Conclusion The heat-band is as effective as the RHB in preventing IPH and its complications in gynaecological laparotomies. PMID:27547112

  5. Mild therapeutic hypothermia in patients resuscitated from out-of-hospital cardiac arrest: A meta-analysis of randomized controlled trials

    PubMed Central

    Villablanca, Pedro A.; Makkiya, Mohammed; Einsenberg, Evann; Briceno, David F.; Panagiota, Christia; Menegus, Mark; Garcia, Mario; Sims, Daniel; Ramakrishna, Harish

    2016-01-01

    Aims: Guidelines recommend mild therapeutic hypothermia (MTH) for survivors of out-of-hospital cardiac arrest (OHCA). However, there is little literature demonstrating a survival benefit. We performed a meta-analysis of randomized controlled trials (RCTs) assessing the efficacy of MTH in patients successfully resuscitated from OHCA. Materials and Methods: Electronic databases were searched for RCT involving MTH in survivors of OHCA, and the results were put through a meta-analysis. The primary endpoint was all-cause mortality, and the secondary endpoint was favorable neurological function. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed using the Mantel–Haenszel method. A fixed-effect model was used and, if heterogeneity (I2) was >40, effects were analyzed using a random model. Results: Six RCT (n = 1400 patients) were included. Overall survival was 50.7%, and favorable neurological recovery was 45.5%. Pooled data demonstrated no significant all-cause mortality (OR, 0.81; 95% CI 0.55–1.21) or neurological recovery (OR, 0.77; 95% CI 0.47–1.24). No evidence of publication bias was observed. Conclusion: This meta-analysis demonstrated that MTH did not confer benefit on overall survival rate and neurological recovery in patients resuscitated from OHCA. PMID:26750667

  6. Adult Onset-Hypothyroidism: Alterations in Hippocampal Field Potentials in the Denate Gyrus are Largely Associated with Anesthesia-Induced Hypothermia

    EPA Science Inventory

    Thyroid hormone (TH) is essential for a number of physiological processes and is particularly critical during nervous system development. The hippocampus is a structure strongly implicated in cognition and is sensitive to developmental hypothyroidism. The impact of TH insuffici...

  7. Amiodarone-induced myxoedema coma.

    PubMed

    Hassan, Syed; Ayoub, Walaa; Hassan, Mona; Wisgerhof, Max

    2014-01-01

    A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 μIU/mL (nl. 0.3-5 μIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8-1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 μg of intravenous levothyroxine in the first 18 h of therapy, and 150 µg intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25-756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease. PMID:24729111

  8. Amiodarone-induced myxoedema coma

    PubMed Central

    Hassan, Syed; Ayoub, Walaa; Hassan, Mona; Wisgerhof, Max

    2014-01-01

    A 62-year-old man was found to have bradycardia, hypothermia and respiratory failure 3 weeks after initiation of amiodarone therapy for atrial fibrillation. Thyroid-stimulating hormone was found to be 168 μIU/mL (nl. 0.3–5 μIU/mL) and free thyroxine (FT4) was <0.2 ng/dL (nl. 0.8–1.8 ng/dL). He received intravenous fluids, vasopressor therapy and stress dose steroids; he was intubated and admitted to the intensive care unit. He received 500 μg of intravenous levothyroxine in the first 18 h of therapy, and 150 µg intravenous daily thereafter. Haemodynamic improvement, along with complete recovery of mental status, occurred after 48 h. Twelve hours after the initiation of therapy, FT4 was 0.96 ng/dL. The patient was maintained on levothyroxine 175 (g POorally daily. A thyroid ultrasound showed diffuse heterogeneity. The 24 hour excretion of iodine was 3657 (mcg (25–756 ( mcg). The only two cases of amiodarone-induced myxoedema coma in the literature report patient death despite supportive therapy and thyroid hormone replacement. This case represents the most thoroughly investigated case of amiodarone-induced myxoedema coma with a history significant for subclinical thyroid disease. PMID:24729111

  9. Antiplatelet efficacy of P2Y12 inhibitors (prasugrel, ticagrelor, clopidogrel) in patients treated with mild therapeutic hypothermia after cardiac arrest due to acute myocardial infarction.

    PubMed

    Bednar, Frantisek; Kroupa, Josef; Ondrakova, Martina; Osmancik, Pavel; Kopa, Milos; Motovska, Zuzana

    2016-05-01

    Survivors after cardiac arrest (CA) due to AMI undergo PCI and then receive dual antiplatelet therapy. Mild therapeutic hypothermia (MTH) is recommended for unconscious patients after CA to improve neurological outcomes. MTH can attenuate the effectiveness of P2Y12 inhibitors by reducing gastrointestinal absorption and metabolic activation. The combined effect of these conditions on the efficacy of P2Y12 inhibitors is unknown. We compared the antiplatelet efficacies of new P2Y12 inhibitors in AMI patients after CA treated with MTH. Forty patients after CA for AMI treated with MTH and received one P2Y12 inhibitor (clopidogrel, prasugrel or ticagrelor) were enrolled in a prospective observational single-center study. Platelet inhibition was measured by VASP (PRI) on days 1, 2, and 3 after drug administration. In-hospital clinical data and 1-year survival data were obtained. The proportion of patients with ineffective platelet inhibition (PRI > 50 %, high on-treatment platelet reactivity) for clopidogrel, prasugrel, and ticagrelor was 77 vs. 19 vs. 1 % on day 1; 77 vs. 17 vs. 0 % on day 2; and 85 vs. 6 vs. 0 % on day 3 (P < 0.001). The platelet inhibition was significantly worse in clopidogrel group than in prasugrel or ticagrelor group. Prasugrel and ticagrelor are very effective for platelet inhibition in patients treated with MTH after CA due to AMI, but clopidogrel is not. Using prasugrel or ticagrelor seems to be a more suitable option in this high-risk group of acute patients. PMID:26340851

  10. Hypothermia During Cardiopulmonary Bypass Increases Need for Inotropic Support but Does Not Impact Inflammation in Children Undergoing Surgical Ventricular Septal Defect Closure.

    PubMed

    Schmitt, Katharina Rose Luise; Fedarava, Katsiaryna; Justus, Georgia; Redlin, Mathias; Böttcher, Wolfgang; Delmo Walter, Eva Maria; Hetzer, Roland; Berger, Felix; Miera, Oliver

    2016-05-01

    Minimizing the systemic inflammatory response caused by cardiopulmonary bypass is a major concern. It has been suggested that the perfusion temperature affects the inflammatory response. The aim of this prospective study was to compare the effects of moderate hypothermia (32°C) and normothermia (36°C) during cardiopulmonary bypass on markers of the inflammatory response and clinical outcomes (time on ventilator) after surgical closure of ventricular septal defects. During surgical closure of ventricular septal defects under cardiopulmonary bypass, 20 children (median age 4.9 months, range 2.3-38 months; median weight 7.2 kg, range 5.2-11.7 kg) were randomized to a perfusion temperature of either 32°C (Group 1, n = 10) or 36°C (Group 2, n = 10). The clinical data and blood samples were collected before cardiopulmonary bypass, directly after aortic cross-clamp release, and 4 and 24 h after weaning from cardiopulmonary bypass. Time on ventilation as primary outcome did not differ between the two groups. Other clinical outcome parameters like fluid balance or length of stay in the intensive care were also similar in the two groups. Compared with Group 2, Group 1 needed significantly higher and longer inotropic support (P < 0.001). In Group 1, two infants had junctional ectopic tachycardia, and another had a pulmonary hypertensive crisis. Perfusion temperature did not influence cytokine release, organ injury, or coagulation. Cardiopulmonary bypass temperature does not influence time on ventilation or inflammatory marker release. However, in the present study, with a small patient cohort, patients operated under hypothermic bypass needed higher and longer inotropic support. The use of hypothermic cardiopulmonary bypass in infants and children should be approached with care. PMID:26581834

  11. Serotoninergic involvement in ethanol-induced alterations of thermoregulation in long-sleep and short-sleep mice.

    PubMed

    French, T A; Weiner, N

    1991-11-01

    The effect of ethanol and pentobarbital on in vivo tryptophan hydroxylase activity and its relationship to drug-induced alterations of thermoregulation was examined in long-sleep (LS) and short-sleep (SS) mice. Serotonin function was measured in both the presence and absence of ethanol or pentobarbital in six discrete brain regions. Differences in basal levels of serotonin, 5-hydroxyindole acetic acid or in vivo tryptophan hydroxylase (TpH) activity were found only in the hypothalamus and dorsal raphe nuclei (SS slightly higher). Ethanol (4.2 g/kg i.p) caused significant reductions in in vivo TpH activity in the dorsal and pontine-medullary raphe nuclei and hypothalamus (putative thermoregulatory areas) in both LS (50-60% decrease) and SS (15-30% decrease) mice, but it had no effect on TpH activity in the striatum, cortex or hippocampus. The greater degree of ethanol-induced reduction in TpH activity in LS mice was associated with a greater degree of hypothermia (LS, 4.2 degrees C vs SS, 2.0 degrees C). Pentobarbital had equivalent effects in LS and SS mice on TpH activity in central nervous system thermoregulatory areas (decreases of 40-60%) and on body temperature (decreases of 6.8-7.5 degrees C). When the mice were given ethanol at an elevated environmental temperature (34 degrees C) the hypothermia was almost abolished completely, but depressant effects on TpH activity remained, suggesting that ethanol-induced decreases in TpH activity were direct effects and not secondary to hypothermia. Alterations in ethanol or pentobarbital elimination did not appear to account for the observed differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1941631

  12. Cardiac Mitochondria l Membrane Stability after Deep Hypothermia using a Xenon Clathrate Cryostasis Protocol – an Electron Microscopy Study

    PubMed Central

    Sheleg, Sergey; Hixon, Hugh; Cohen, Bruce; Lowry, David; Nedzved, Mikhail

    2008-01-01

    We investigated a new cryopreservation method using xenon, a clathrate-forming gas, under medium pressure (100psi). The objective of the study was to determine whether this cryostasis protocol could protect cardiac mitochondria at cryogenic temperatures (below 100 degrees Celsius).We analyzed transmission electron microscopy images to obtain information about changes in mitochondrial morphology induced by cryopreservation of the hearts. Our data showed absence of mitochondrial swelling, rupture of inner and outer membranes, and leakage of mitochondrial matrix into the cytoplasm after applying this cryostasis protocol. The electron microscopy results provided the first evidence that a cryostasis protocol using xenon as a clathrate-forming gas under pressure may have protective effects on intracellular membranes. This cryostasis technology may find applications in developing new approaches for long-term cryopreservation protocols. PMID:18787624

  13. Suppression of Dendritic Cell-Derived IL-12 by Endogenous Glucocorticoids Is Protective in LPS-Induced Sepsis

    PubMed Central

    Mittelstadt, Paul R.; Castro, Ehydel; Ashwell, Jonathan D.

    2015-01-01

    Sepsis, an exaggerated systemic inflammatory response, remains a major medical challenge. Both hyperinflammation and immunosuppression are implicated as causes of morbidity and mortality. Dendritic cell (DC) loss has been observed in septic patients and in experimental sepsis models, but the role of DCs in sepsis, and the mechanisms and significance of DC loss, are poorly understood. Here, we report that mice with selective deletion of the glucocorticoid receptor (GR) in DCs (GRCD11c-cre) were highly susceptible to LPS-induced septic shock, evidenced by elevated inflammatory cytokine production, hypothermia, and mortality. Neutralizing anti-IL-12 antibodies prevented hypothermia and death, demonstrating that endogenous GC-mediated suppression of IL-12 is protective. In LPS-challenged GRCD11c-cre mice, CD8+ DCs were identified as the major source of prolonged IL-12 production, which correlated with elevations of NK cell-derived IFN-γ. In addition, the loss of GR in CD11c+ cells rescued LPS-induced loss of CD8+ DCs but not other DC subsets. Unlike wild-type animals, exposure of GRCD11c-cre mice to low-dose LPS did not induce CD8+ DC loss or tolerance to subsequent challenge with high dose, but neutralization of IL-12 restored the ability of low-dose LPS to tolerize. Therefore, endogenous glucocorticoids blunt LPS-induced inflammation and promote tolerance by suppressing DC IL-12 production. PMID:26440998

  14. Simulation of scalp cooling by external devices for prevention of chemotherapy-induced alopecia.

    PubMed

    Pliskow, Bradley; Mitra, Kunal; Kaya, Mehmet

    2016-02-01

    Hypothermia of the scalp tissue during chemotherapy treatment (scalp cooling) has been shown to reduce or prevent chemotherapy-induced hair loss. In this study, numerical models are developed to investigate the interaction between different types of external scalp cooling devices and the human scalp tissue. This work focuses on improving methods of modeling scalp cooling devices as it relates specifically to the prevention of chemotherapy-induced alopecia. First, the cooling power needed for any type of device to achieve therapeutic levels of scalp hypothermia is investigated. Subsequently, two types of scalp cooling devices are simulated: a pre-cooled/frozen cap design and a liquid-cooled cap design. For an average patient, simulations show that 38.5W of heat must be extracted from the scalp tissue for this therapy in order to cool the hair follicle to 22°C. In practice, the cooling power must be greater than this amount to account for thermal losses of the device. Simulations show that pre-cooled and liquid-cooled cap designs result in different tissue temperatures over the course of the procedure. However, it is the temperature of the coolant that largely determines the resulting tissue temperature. Simulations confirm that the thermal resistance of the hair/air layer has a large impact on the resulting tissue temperatures. The results should be correlated with experimental data as an effort to determine the optimal parameter choices for this model. PMID:26857974

  15. Microwave radiation (2450 MHz) alters the endotoxin-induced hypothermic response of rats

    SciTech Connect

    Smialowicz, R.J.; Compton, K.L.; Riddle, M.M.; Rogers, R.R.; Brugnolotti, P.L.

    1980-01-01

    The parenteral administration of bacterial endotoxin to rats causes a hypothermia that is maximal after approximately 90 minutes. When endotoxin-injected rats were held in a controlled environment at 22 degree C and 50% relative humidity and exposed for 90 minutes to microwaves (2450 MHz, CW) at 1 mW/cm2, significant increases were observed in body temperature compared with endotoxin-treated, sham-irradiated rats. The magnitude of the response was related to power density (10 mW/cm2 greater than 5 mW/cm2 greater than 1 mW/cm2). Saline-injected rats exposed for 90 minutes at 5 mW/cm2 (specific absorption rate approximately 1.0 mW/g) showed no significant increase in body temperature compared with saline-injected, sham-irradiated rats. The hypothermia induced by endotoxin in rats was also found to be affected by ambient temperature alone. Increases in ambient temperature above 22 degree C in the absence of microwaves caused a concomitant increase in body temperature. This study reveals that subtle microwave heating is detectable in endotoxin-treated rats that have impaired thermoregulatory capability. These results indicate that the interpretation of microwave-induced biological effects observed in animals at comparable rates and levels of energy absorption should include a consideration of the thermogenic potential of microwave.

  16. Neurological Outcome Scale for Traumatic Brain Injury: III. Criterion-Related Validity and Sensitivity to Change in the NABIS Hypothermia-II Clinical Trial

    PubMed Central

    Wilde, Elisabeth A.; Moretti, Paolo; MacLeod, Marianne C.; Pedroza, Claudia; Drever, Pamala; Fourwinds, Sierra; Frisby, Melisa L.; Beers, Sue R.; Scott, James N.; Hunter, Jill V.; Traipe, Elfrides; Valadka, Alex B.; Okonkwo, David O.; Zygun, David A.; Puccio, Ava M.; Clifton, Guy L.

    2013-01-01

    Abstract The Neurological Outcome Scale for Traumatic Brain Injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. Participants were 16–45 years of age with severe TBI assessed at 1, 3, 6, and 12 months postinjury. For analysis of criterion-related validity (concurrent and predictive), Spearman's rank-order correlations were calculated between the NOS-TBI and the Glasgow Outcome Scale (GOS), GOS-Extended (GOS-E), Disability Rating Scale (DRS), and Neurobehavioral Rating Scale-Revised (NRS-R). Concurrent validity was demonstrated through significant correlations between the NOS-TBI and GOS, GOS-E, DRS, and NRS-R measured contemporaneously at 3, 6, and 12 months postinjury (all p<0.0013). For prediction analyses, the multiplicity-adjusted p value using the false discovery rate was <0.015. The 1-month NOS-TBI score was a significant predictor of outcome in the GOS, GOS-E, and DRS at 3 and 6 months postinjury (all p<0.015). The 3-month NOS-TBI significantly predicted GOS, GOS-E, DRS, and NRS-R outcomes at 6 and 12 months postinjury (all p<0.0015). Sensitivity to change was analyzed using Wilcoxon's signed rank-sum test of subsamples demonstrating no change in the GOS or GOS-E between 3 and 6 months. The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research. PMID:23617608

  17. Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus

    PubMed Central

    Rock, E M; Kopstick, R L; Limebeer, C L; Parker, L A

    2013-01-01

    BACKGROUND AND PURPOSE We evaluated the anti-emetic and anti-nausea properties of the acid precursor of Δ9-tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models. EXPERIMENTAL APPROACH We investigated the effect of THCA on lithium chloride- (LiCl) induced conditioned gaping (nausea-induced behaviour) to a flavour, and context (a model of anticipatory nausea) in rats, and on LiCl-induced vomiting in Suncus murinus. Furthermore, we investigated THCA's ability to induce hypothermia and suppress locomotion [rodent tasks to assess cannabinoid1 (CB1) receptor agonist-like activity], and measured plasma and brain THCA and THC levels. We also determined whether THCA's effect could be blocked by pretreatment with SR141716 (SR, a CB1 receptor antagonist). KEY RESULTS In rats, THCA (0.05 and/or 0.5 mg·kg−1) suppressed LiCl-induced conditioned gaping to a flavour and context; the latter effect blocked by the CB1 receptor antagonist, SR, but not by the 5-hydroxytryptamine-1A receptor antagonist, WAY100635. In S. murinus, THCA (0.05 and 0.5 mg·kg−1) reduced LiCl-induced vomiting, an effect that was reversed with SR. A comparatively low dose of THC (0.05 mg·kg−1) did not suppress conditioned gaping to a LiCl-paired flavour or context. THCA did not induce hypothermia or reduce locomotion, indicating non-CB1 agonist-like effects. THCA, but not THC was detected in plasma samples. CONCLUSIONS AND IMPLICATIONS THCA potently reduced conditioned gaping in rats and vomiting in S. murinus, effects that were blocked by SR. These data suggest that THCA may be a more potent alternative to THC in the treatment of nausea and vomiting. PMID:23889598

  18. Pilot randomized trial of therapeutic hypothermia with serial cranial ultrasound and 18-22 month follow-up for neonatal encephalopathy in a low resource hospital setting in uganda: study protocol

    PubMed Central

    2011-01-01

    Background There is now convincing evidence that in industrialized countries therapeutic hypothermia for perinatal asphyxial encephalopathy increases survival with normal neurological function. However, the greatest burden of perinatal asphyxia falls in low and mid-resource settings where it is unclear whether therapeutic hypothermia is safe and effective. Aims Under the UCL Uganda Women's Health Initiative, a pilot randomized controlled trial in infants with perinatal asphyxia was set up in the special care baby unit in Mulago Hospital, a large public hospital with ~20,000 births in Kampala, Uganda to determine: (i) The feasibility of achieving consent, neurological assessment, randomization and whole body cooling to a core temperature 33-34°C using water bottles (ii) The temperature profile of encephalopathic infants with standard care (iii) The pattern, severity and evolution of brain tissue injury as seen on cranial ultrasound and relation with outcome (iv) The feasibility of neurodevelopmental follow-up at 18-22 months of age Methods/Design Ethical approval was obtained from Makerere University and Mulago Hospital. All infants were in-born. Parental consent for entry into the trial was obtained. Thirty-six infants were randomized either to standard care plus cooling (target rectal temperature of 33-34°C for 72 hrs, started within 3 h of birth) or standard care alone. All other aspects of management were the same. Cooling was performed using water bottles filled with tepid tap water (25°C). Rectal, axillary, ambient and surface water bottle temperatures were monitored continuously for the first 80 h. Encephalopathy scoring was performed on days 1-4, a structured, scorable neurological examination and head circumference were performed on days 7 and 17. Cranial ultrasound was performed on days 1, 3 and 7 and scored. Griffiths developmental quotient, head circumference, neurological examination and assessment of gross motor function were obtained at 18

  19. Therapeutic hypothermia following perinatal asphyxia

    PubMed Central

    Edwards, A D; Azzopardi, D V

    2006-01-01

    Well constructed and carefully analysed trials of hypothermic neural rescue therapy for infants with neonatal encephalopathy have recently been reported. The data suggest that either selective head cooling or total body cooling reduces the combined chance of death or disability after birth asphyxia. However, as there are still unanswered questions about these treatments, many may still feel that further data are needed before health care policy can be changed to make cooling the standard of care for all babies with suspected birth asphyxia. PMID:16492950

  20. Cardiac-specific VLCAD deficiency induces dilated cardiomyopathy and cold intolerance

    PubMed Central

    Xiong, Dingding; He, Huamei; James, Jeanne; Tokunaga, Chonan; Powers, Corey; Huang, Yan; Osinska, Hanna; Towbin, Jeffrey A.; Purevjav, Enkhsaikhan; Balschi, James A.; Javadov, Sabzali; McGowan, Francis X.; Strauss, Arnold W.

    2013-01-01

    The very long-chain acyl-CoA dehydrogenase (VLCAD) enzyme catalyzes the first step of mitochondrial β-oxidation. Patients with VLCAD deficiency present with hypoketotic hypoglycemia and cardiomyopathy, which can be exacerbated by fasting and/or cold stress. Global VLCAD knockout mice recapitulate these phenotypes: mice develop cardiomyopathy, and cold exposure leads to rapid hypothermia and death. However, the contribution of different tissues to development of these phenotypes has not been studied. We generated cardiac-specific VLCAD-deficient (cVLCAD−/−) mice by Cre-mediated ablation of the VLCAD in cardiomyocytes. By 6 mo of age, cVLCAD−/− mice demonstrated increased end-diastolic and end-systolic left ventricular dimensions and decreased fractional shortening. Surprisingly, selective VLCAD gene ablation in cardiomyocytes was sufficient to evoke severe cold intolerance in mice who rapidly developed severe hypothermia, bradycardia, and markedly depressed cardiac function in response to fasting and cold exposure (+5°C). We conclude that cardiac-specific VLCAD deficiency is sufficient to induce cold intolerance and cardiomyopathy and is associated with reduced ATP production. These results provide strong evidence that fatty acid oxidation in myocardium is essential for maintaining normal cardiac function under these stress conditions. PMID:24285112

  1. Role(s) of IL-2 inducible T cell kinase and Bruton's tyrosine kinase in mast cell response to lipopolysaccharide.

    PubMed

    Huang, Weishan; August, Avery

    2016-06-01

    Mast cells play critical roles during immune responses to the bacterial endotoxin lipopolysaccharide (LPS) that can lead to fatal septic hypothermia [1], [2], [3]. IL-2 inducible T cell kinase (ITK) and Bruton's tyrosine kinase (BTK) are non-receptor tyrosine kinases that act downstream of numerous receptors, and have been shown to modulate mast cell responses downstream of FcεRIα [4], however, their roles in regulating mast cell responses to endotoxic stimuli were unclear. We found that the absence of ITK and BTK alters the mast cell response to LPS, and leads to enhanced pro-inflammatory cytokine production by mast cells and more severe LPS-induced hypothermia in mice [5]. Here, we detail our investigation using microarray analysis to study the transcriptomic profiles of mast cell responses to LPS, and the roles of ITK and/or BTK expression in this process. Mouse whole genome array data of WT, Itk (-/-) , Btk (-/-) , and Itk (-/-)  Btk (-/-) bone marrow-derived mast cells (BMMCs) stimulated by PBS (control) or LPS for 1 h were used in our latest research article [5] and is available in the Gene Expression Omnibus under accession number GSE64287. PMID:27081634

  2. The onset of daily torpor is regulated by the same low body mass in lean mice and in mice with diet-induced obesity

    PubMed Central

    Solymár, Margit; Pétervári, Erika; Balaskó, Márta; Szelényi, Zoltán

    2015-01-01

    Effects of reducing body mass on body core temperature and locomotor activity of mice originally kept on conventional rodent diet (Group-1) were compared to those made obese by feeding them a high-fat diet (Group-2), both groups being kept at a cool ambient temperature. Based on earlier experience, threshold torpor core temperature of 31° was chosen as the endpoint to decreasing body mass. It was hypothesized that the onset of this hypothermia develops in obese mice only when their body mass approaches a similar low body mass as in lean mice. Mice in Group-1 maintained nocturnal core temperature but developed marked daytime hypothermia of 30–31°C with their body mass approaching 20 g by this time. Mice in Group-2 could maintain normal circadian temperature rhythm for 3 weeks before similar daytime hypothermia started to develop while their body mass dropped also to about 20 g. Mice belonging to Group-1 or Group-2 could regain original body mass after re-feeding with the original diet within 2 days or 5 weeks, respectively. In the course of the development of daily torpor, nighttime normothermia was accompanied by progressive increases in locomotor activity in both groups of mice. It is concluded that in mice a marked fall of daytime body core temperature is only induced when a similar low critical body mass is reached, irrespective of the initial body mass. In other words, in both groups of mice the nutritional state determines the threshold for the thermoregulatory change during torpor.

  3. A comparative pharmacological investigation of three samples of 'Guduchi ghrita' for adaptogenic activity against forced swimming induced gastric ulceration and hematological changes in albino rats

    PubMed Central

    Savrikar, Shriram S.; Dole, Vilas; Ravishankar, B.; Shukla, Vinay J.

    2010-01-01

    This study was undertaken to investigate the impact of formulation factors and adjuvants on the expression of biological activity of Tinospora cordifolia (Willd.) Miers. The adaptogenic effect of three samples of Guduchi ghrita, prepared using plain ghee (clarified butter) obtained from three different sources was studied in albino rats and compared with expressed juice of stem of Guduchi. The test preparations were evaluated against forced–swimming induced hypothermia, gastric ulceration and changes in the hematological parameters. The test drug given in the form of 'ghrita' produced better effect in comparison to the expressed juice. Among the three 'ghrita' preparations evaluated, only the 'Solapur Guduchi ghrita' (SGG) was found to produce significant inhibition of stress hypothermia and gastric ulceration. The other two preparations 'Nanded Guduchi ghrita' (NGG), and 'Wardha Guduchi ghrita' (WGG) could produce only a marginal effect. In hematological parameters 'Guduchi' juice produced better reversal of the stress-induced changes in comparison to the test 'ghrita' preparations. The present study provides evidence highlighting the importance of formulation factors for the expression of biological activity. PMID:20814518

  4. Finger cold-induced vasodilation: a review.

    PubMed

    Daanen, H A M

    2003-06-01

    Cold-induced vasodilation (CIVD) in the finger tips generally occurs 5-10 min after the start of local cold exposure of the extremities. This phenomenon is believed to reduce the risk of local cold injuries. However, CIVD is almost absent during hypothermia, when survival of the organism takes precedence over the survival of peripheral tissue. Subjects that are often exposed to local cold (e.g. fish filleters) develop an enhanced CIVD response. Also, differences between ethnic groups are obvious, with black people having the weakest CIVD response. Many other factors affect CIVD, such as diet, alcohol consumption, altitude, age and stress. CIVD is probably caused by a sudden decrease in the release of neurotransmitters from the sympathetic nerves to the muscular coat of the arterio-venous anastomoses (AVAs) due to local cold. AVAs are specific thermoregulatory organs that regulate blood flow in the cold and heat. Their relatively large diameter enables large amounts of blood to pass and convey heat to the surrounding tissue. Unfortunately, information on the quantity of AVAs is lacking, which makes it difficult to estimate the full impact on peripheral blood flow. This review illustrates the thermospecificity of the AVAs and the close link to CIVD. CIVD is influenced by many parameters, but controlled experiments yield information on how CIVD protects the extremities against cold injuries. PMID:12712346

  5. Effect of temperature on isoprenaline- and barium-induced slow action potentials in guinea-pig ventricular strips.

    PubMed

    Manzini, S; Parlani, M; Martucci, E; Maggi, C A; Meli, A

    1986-01-01

    The effect of variation in temperature (37-32 and 27 degrees C) on electrical and mechanical activity of depolarized and isoprenaline- or barium-reactivated guinea pig ventricular strips was studied. Lowering the temperature brings a marked prolongation of isoprenaline-induced slow action potentials. In addition the maximal rate of depolarization was strongly reduced at lower temperatures. These effects were observed at an extracellular Ca2+ concentration of either 0.9 or 2.5 mM. The accompanying mechanical activities was significantly increased by reduction in temperature. Barium-induced slow action potentials were similarly affected by temperature variations. These observations suggest that hypothermia exert a sort of calcium antagonistic action probably coupled to a reduction of repolarizing outward potassium currents. PMID:2430855

  6. Hypergravity-Induced Changes in Hematological and Lymphocyte Function Parameters in a Mouse Model

    NASA Technical Reports Server (NTRS)

    Gridley, Daila S.; Miller, Glen M.; Nelson, Gregory A.; Pecaut, Michael J.

    2003-01-01

    The purpose of this study was to quantify hypergravity-induced changes in hematological and lymphocyte characteristics. Mice were subjected to 1, 2, and 3G and euthanized on days 1 , 4, 7, 10, and 21. The data show that increased gravitational force resulted in persistent hypothermia. Red blood cell (RBC) counts, hematocrit, and hemoglobin were reduced by day 21, whereas hemoglobin and RBC volume were low at most times of measurement. A transient increase was noted in platelet numbers in the 3G group. Fluctuations in spontaneous blastogenesis of lymphocytes were dependent upon centrifugation time and not gravity. Changes in splenocyte responses to T and B cell mitogens due to gravity were also noted. Cytokine production was primarily affected during the first week; IL-2, IL-4 and TNF-alpha were increased, whereas IFN-gamma was decreased. These findings indicate that altered gravity can influence both hematological and functional variables that may translate into serious health consequences.

  7. Dimethyl Sulfoxide Induces Both Direct and Indirect Tau Hyperphosphorylation

    PubMed Central

    Julien, Carl; Marcouiller, François; Bretteville, Alexis; El Khoury, Noura B.; Baillargeon, Joanie; Hébert, Sébastien S.; Planel, Emmanuel

    2012-01-01

    Dimethyl sulfoxide (DMSO) is widely used as a solvent or vehicle for biological studies, and for treatment of specific disorders, including traumatic brain injury and several forms of amyloidosis. As Alzheimer’s disease (AD) brains are characterized by deposits of β-amyloid peptides, it has been suggested that DMSO could be used as a treatment for this devastating disease. AD brains are also characterized by aggregates of hyperphosphorylated tau protein, but the effect of DMSO on tau phosphorylation is unknown. We thus investigated the impact of DMSO on tau phosphorylation in vitro and in vivo. One hour following intraperitoneal administration of 1 or 2 ml/kg DMSO in mice, no change was observed in tau phosphorylation. However, at 4 ml/kg, tau was hyperphosphorylated at AT8 (Ser202/Thr205), PHF-1 (Ser396/Ser404) and AT180 (Thr231) epitopes. At this dose, we also noticed that the animals were hypothermic. When the mice were maintained normothermic, the effect of 4 ml/kg DMSO on tau hyperphosphorylation was prevented. On the other hand, in SH-SY5Y cells, 0.1% DMSO induced tau hyperphosphorylation at AT8 and AT180 phosphoepitopes in normothermic conditions. Globally, these findings demonstrate that DMSO can induce tau hyperphosphorylation indirectly via hypothermia in vivo, and directly in vitro. These data should caution researchers working with DMSO as it can induce artifactual results both in vivo and in vitro. PMID:22768202

  8. Renal Insufficiency and Early Bystander CPR Predict In-Hospital Outcomes in Cardiac Arrest Patients Undergoing Mild Therapeutic Hypothermia and Cardiac Catheterization: Return of Spontaneous Circulation, Cooling, and Catheterization Registry (ROSCCC Registry)

    PubMed Central

    Chelvanathan, Anjala; Allen, David; Bews, Hilary; Ducas, John; Minhas, Kunal; Ravandi, Amir; Jassal, Davinder S.; Hussain, Farrukh

    2016-01-01

    Objective. Out of hospital cardiac arrest (OHCA) patients are a critically ill patient population with high mortality. Combining mild therapeutic hypothermia (MTH) with early coronary intervention may improve outcomes in this population. The aim of this study was to evaluate predictors of mortality in OHCA patients undergoing MTH with and without cardiac catheterization. Design. A retrospective cohort of OHCA patients who underwent MTH with catheterization (MTH + C) and without catheterization (MTH + NC) between 2006 and 2011 was analyzed at a single tertiary care centre. Predictors of in-hospital mortality and neurologic outcome were determined. Results. The study population included 176 patients who underwent MTH for OHCA. A total of 66 patients underwent cardiac catheterization (MTH + C) and 110 patients did not undergo cardiac catheterization (MTH + NC). Immediate bystander CPR occurred in approximately half of the total population. In the MTH + C and MTH + NC groups, the in-hospital mortality was 48% and 78%, respectively. The only independent predictor of in-hospital mortality for patients with MTH + C, after multivariate analysis, was baseline renal insufficiency (OR = 8.2, 95% CI 1.8–47.1, and p = 0.009). Conclusion. Despite early cardiac catheterization, renal insufficiency and the absence of immediate CPR are potent predictors of death and poor neurologic outcome in patients with OHCA. PMID:26885436

  9. Study of therapeutic hypothermia (32 to 35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial): outcome of the pilot phase of the trial

    PubMed Central

    2013-01-01

    Background Clinical trials in traumatic brain injury (TBI) are challenging. Previous trials of complex interventions were conducted in high-income countries, reported long lead times for site setup and low screened-to-recruitment rates. In this report we evaluate the internal pilot phase of an international, multicentre TBI trial of a complex intervention to assess: design and implementation of an online case report form; feasibility of recruitment (sites and patients); feasibility and effectiveness of delivery of the protocol. Methods All aspects of the pilot phase of the trial were conducted as for the main trial. The pilot phase had oversight by independent Steering and Data Monitoring committees. Results Forty sites across 12 countries gained ethical approval. Thirty seven of 40 sites were initiated for recruitment. Of these, 29 had screened patients and 21 randomized at least one patient. Lead times to ethics approval (6.8 weeks), hospital approval (18 weeks), interest to set up (61 weeks), set up to screening (11 weeks), and set up to randomization (31.6 weeks) are comparable with other international trials. Sixteen per cent of screened patients were eligible. We found 88% compliance rate with trial protocol. Conclusion The pilot data demonstrated good feasibility for this large international multicentre randomized controlled trial of hypothermia to control intracranial pressure. The sample size was reduced to 600 patients because of homogeneity of the patient group and we showed an optimized cooling intervention could be delivered. Trial registration Current Controlled Trials: ISRCTN34555414. PMID:24004918

  10. Antagonism of corticotropin-releasing hormone alters serotonergic-induced changes in brain temperature, but not sleep, of rats.

    PubMed

    Imeri, Luca; Bianchi, Susanna; Opp, Mark R

    2005-10-01

    Serotonin is involved in many physiological processes, including the regulation of sleep and body temperature. Administration into rats of low doses (25, 50 mg/kg) of the 5-HT precursor l-5-hydroxytryptophan (5-HTP) at the beginning of the dark period of the 12:12-h light-dark cycle initially increases wakefulness. Higher doses (75, 100 mg/kg) increase nonrapid eye movement (NREM) sleep. The initial enhancement of wakefulness after low-dose 5-HTP administration may be a direct action of 5-HT in brain or due to 5-HT-induced activation of other arousal-promoting systems. One candidate arousal-promoting system is corticotropin-releasing hormone (CRH) and the hypothalamic-pituitary-adrenal axis. Serotonergic activation by 5-HTP at the beginning of the dark period also induces hypothermia. Because sleep and body temperature are influenced by circadian factors, one aim of this study was to determine responses to 5-HTP when administered at a different circadian time, the beginning of the light period. Results obtained show that all doses of 5-HTP (25-100 mg/kg) administered at light onset initially increase wakefulness; NREM sleep increases