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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We performed extended aortic arch anastomosis, which was so called EAA procedure, for Coarctation of the Aorta (CoA) with hypoplastic aortic arch (HAA) and interruption of the aortic arch (IAA) in 17 infants under three months of age. The proximal anastomosis site was extended into ascending aorta in order that we could make non-obstructive pathway of systemic flow. During anastomosis, we employed mild systemic hypothermia and topical cooling of head and lumber lesion. Satisfactory anastomoses were performed without any neurological and renal complications except one case. Postoperative Doppler echographic evaluation revealed that the mean peak flow velocities at anastomotic site were under 2.0 m/sec at 1 and 2 years after surgery. We concluded that EAA procedure was useful for CoA with HAA and IAA in early infancy.
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PMID:[Extended aortic arch anastomosis for coarctation of the aorta and interruption of the aortic arch in early infancy]. 815 69

Although profound hypothermia has been used for decades to protect the human brain from hypoxic or ischemic insults, little is known about the underlying mechanism. We therefore report the first characterization of the effects of moderate (30 degrees C) and profound hypothermia (12 degrees to 20 degrees C) on excitotoxicity in cultured cortical neurons exposed to excitatory amino acids (EAA; glutamate, N-methyl-D-aspartate [NMDA], AMPA, or kainate) at different temperatures (12 degrees to 37 degrees C). Cooling neurons to 30 degrees C and 20 degrees C was neuroprotective, but cooling to 12 degrees C was toxic. The extent of protection depended on the temperature, the EAA receptor agonist employed, and the duration of the EAA challenge. Neurons challenged briefly (5 minutes) with all EAA were protected, as were neurons challenged for 60 minutes with NMDA, AMPA, or kainate. The protective effects of hypothermia (20 degrees and 30 degrees C) persisted after rewarming to 37 degrees C, but rewarming from 12 degrees C was deleterious. Surprisingly, however, prolonged (60 minutes) exposures to glutamate unmasked a temperature-insensitive component of glutamate neurotoxicity that was not seen with the other, synthetic EAA; this component was still mediated via NMDA receptors, not by ionotropic or metabotropic non-NMDA receptors. The temperature-insensitivity of glutamate toxicity was not explained by effects of hypothermia on EAA-evoked [Ca2+]i increases measured using high- and low-affinity Ca2+ indicators, nor by effects on mitochondrial production of reactive oxygen species. This first characterization of excitotoxicity at profoundly hypothermic temperatures reveals a previously unnoticed feature of glutamate neurotoxicity unseen with the other EAA, and also suggests that hypothermia protects the brain at the level of neurons by blocking, rather than slowing, excitotoxicity.
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PMID:Characterization of neuroprotection from excitotoxicity by moderate and profound hypothermia in cultured cortical neurons unmasks a temperature-insensitive component of glutamate neurotoxicity. 970 46

We have previously reported that a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, DL-[E]-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 37849), produces stereotyped behaviors and hyperlocomotion in amygdala kindled rats at doses which do not induce such phencyclidine (PCP)-like behaviors in nonkindled rats, indicating that kindling predisposes rats to such adverse effects of competitive NMDA receptor antagonists. From these data we predicted that epileptic patients may exhibit a hypersensitivity to PCP-like adverse effects of competitive NMDA receptor antagonists, which was subsequently confirmed in a clinical trial with D-CPPene (SDZ EAA-494; 3-(2-carboxypiperazine-4-yl)propenyl-1-phosphonate). For further exploration of the functional alterations in NMDA receptor responsiveness produced by kindling, we studied whether the enhanced susceptibility of amygdala-kindled rats to PCP-like adverse effects of CGP 37849 is also observed with D-CPPene. Furthermore, we determined whether the enhanced susceptibility of kindled rats to such adverse effects occurs only after relatively short intervals following the last seizure, as used in our previous study, or is a more permanent phenomenon. For this purpose, we compared adverse effects in kindled rats not only with naive (non-implanted) controls, as done in our previous study, but used electrode-implanted nonkindled rats as an additional control to assess the possible bias of mere electrode-implantation. In addition, we studied whether the enhanced susceptibility to NMDA receptor antagonists of electrically kindled rats is also present in chemically kindled animals. In some experiments, the PCP-like uncompetitive NMDA receptor antagonist MK-801 (dizocilpine) was included for comparison. In amygdala kindled rats, D-CPPene produced significantly more stereotyped behaviors than in electrode-implanted or naive nonkindled controls. The enhanced sensitivity of electrically kindled rats to PCP-like stereotypies induced by D-CPPene was observed both 7 and 180 days after the last kindled seizure, indicating a long-lasting if not permanent hypersensitivity to these adverse effects. In addition, more intense circling was observed in amygdala kindled rats, whereas hyperlocomotion only tended to be more intense after D-CPPene in kindled rats. These alterations in D-CPPene-induced behaviors were not observed after chemical kindling with pentylenetetrazole, but D-CPPene induced significantly less hypothermia in chemically kindled rats both 7 and 70 days after the last seizure. The data demonstrate that kindling produces long-lasting alterations in some adverse effects of D-CPPene, substantiating that epileptogenesis as initiated by kindling renders the brain more susceptible to PCP-like behavioral side effects of competitive NMDA receptor antagonists.
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PMID:Electrical but not chemical kindling increases sensitivity to some phencyclidine-like behavioral effects induced by the competitive NMDA receptor antagonist D-CPPene in rats. 972 48

In order to elucidate the mechanisms of release of EAAs and their excitotoxicity in cerebral contusion, cortical contusion was produced in the rat parietal cortex, and the changes in extracellular levels of EAAs in the central and peripheral areas of contusion were investigated using microdialysis. The cortical contusion induced a rapid increase in dialysate concentration of glutamate ([Glu]d) from a baseline level of 4.6+/-2.8 microM to a maximum level of 36.3+/-12.8 microM. This elevation of glutamate was significantly attenuated by mild hypothermia (32 degrees C for 90 min, comprising 20 min before and 70 min after the injury induction) in the peripheral area of contusion (p < 0.01) but not in the central area. Histological evaluations revealed that the hypothermia reduced the necrosis volume of contusion to 38.3% of that in the normothermic control (p < 0.01). In situ administration of Co2+, an inhibitor of Co2+-dependent exocytotic release of EAAs from the nerve terminals, via the microdialysis system, also attenuated the [Glu]d elevation following cortical contusion, in the peripheral area of contusion (p < 0.01) but not in the central area. These findings indicate that cerebral contusion involves heterogeneous and complex mechanisms of EAA release into the extracellular space. The release of EAAs in the contusion core was nonsensitive to hypothermia and Co2+ administration, suggesting that such EAA release was related to primary disruption of the cell membrane or vascular wall by the physical force of the head trauma, resulting in leakage of EAAs from the metabolic pool in the cytosole or blood stream. In contrast, in the peripheral area, the effectiveness of hypothermia and Co2+ administration implied a presynaptic mechanism of EAA release, which consisted, at least in part, of Ca2+-dependent exocytotic EAA release from depolarized nerve terminals. The EAAs released in the contusion core may diffuse towards a peripheral direction and act on the postsynaptic receptors, causing neuronal depolarization. Such a diffusion-reaction process appears to induce additional release of EAAs from the depolarized nerve terminals. Hypothermia may block this diffusion-reaction process and eventually reduce the contusion volume.
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PMID:Mechanisms of excitatory amino acid release in contused brain tissue: effects of hypothermia and in situ administration of Co2+ on extracellular levels of glutamate. 975 13

Traumatic brain injury in the United States is a serious health problem: it is a significant factor in approximately half of all trauma-related deaths, and, leads to persistent, long-term neurologic dysfunction in survivors. Physiological changes that accompany brain trauma such as cardiovascular alterations, hypercapnia, hypoxiaischemia, metabolic dysfunction, and alterations in the endogenous neurochemical systems are associated with poor clinical outcome. Using a variety of animal models, experimental studies have begun to elucidate these neurochemical disturbances that underlie the behavioral deficits and the pathologic outcome. Modification of the post-traumatic neurochemical milieu can promote functional recovery. While a number of currently available pharmaceutical compounds have been reported to be effective in various animal models of TBI, their utility in the clinical setting has been disappointing [119]. New hope has arisen for the treatment of TBI, based upon new research findings regarding the development of novel pharmacological therapies for brain trauma. Reduction of brain temperature can maintain relative tissue homeostasis by lowering metabolic activity. Hypothermia has been attempted in patients over the past 50 years and recent experimental evidence suggests that posttraumatic hypothermia can attenuate EAA release and free-radical production [120]. In animal models, hypothermic treatment has attenuated post-traumatic neurologic motor dysfunction [121,122], improved histopathologic damage [123,124], and reduced the extent of cytoskeletal damage [120]. In addition, the armamentarium of potentially neuroprotective compounds, which has increased rapidly in the recent years, provides promising pharmacological therapies for the treatment of TBI.
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PMID:Pharmacotherapy for traumatic brain injury: a review. 983

In urethane-chloralose anaesthetized, neuromuscularly blocked, artificially ventilated rats, we demonstrated that activation of carotid chemoreceptors inhibits the elevated levels of brown adipose tissue (BAT) sympathetic nerve activity (SNA) evoked by hypothermia, by microinjection of prostaglandin E2 into the medial preoptic area or by disinhibition of neurones in the raphe pallidus area (RPa). Peripheral chemoreceptor stimulation with systemic administration of NaCN (50 microg in 0.1 ml) or with hypoxic ventilation (8% O2-92% N2, 30 s) completely inhibited BAT SNA. Arterial chemoreceptor-evoked inhibition of BAT SNA was eliminated by prior bilateral transections of the carotid sinus nerves or by prior inhibition of neurones within the commissural nucleus tractus solitarii (commNTS) with glycine (40 nmol/80 nl) or with the GABAA receptor agonist muscimol (160 pmol/80 nl; 77 +/- 10% attenuation), or by prior blockade of ionotropic excitatory amino acid receptors in the commNTS with kynurenate (8 nmol/80 nl; 82 +/- 10% attenuation). Furthermore, activation of commNTS neurones following local microinjection of bicuculline (30 pmol/60 nl) completely inhibited the elevated level of BAT SNA resulting from disinhibition of neurones in the RPa. These results demonstrate that hypoxic stimulation of arterial chemoreceptor afferents leads to an inhibition of BAT SNA and BAT thermogenesis through an EAA-mediated activation of second-order, arterial chemoreceptor neurones in the commNTS. Peripheral chemoreceptor-evoked inhibition of BAT SNA could directly contribute to (or be permissive for) the hypoxia-evoked reductions in body temperature and oxygen consumption that serve as an adaptive response to decreased oxygen availability.
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PMID:Hypoxic activation of arterial chemoreceptors inhibits sympathetic outflow to brown adipose tissue in rats. 1587 45