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

The basic physiologic characteristics of acid-base equilibria during hypothermia were briefly reviewed. By graphic analysis, four possible clinical strategies for managing the acid-base status of the patient undergoing H-CPB were documented. The effect of hemodilution on buffer capacity was charted in a manner applicable to common current operative procedures. During hypothermia for cardiac operations as presently conducted, the perfusionist is in control of the temperature of the body and the perfusion preservation of the body and brain; the surgeon must assume responsibility for preservation of the heart. The literature pertinent to the relationship of the acid-base state to the functions and structural preservation of the heart and brain during the conditions of cooling to and rewarming from deep hypothermia associated with cardiopulmonary bypass, aortic cross clamping, cardioplegia and total circulatory arrest have been reviewed. The evidence is overwhelming that myocardial anoxia caused by aortic occlusion or total circulatory arrest at any temperature to 15 degrees C. result in progressive acidosis which, of itself, is myotoxic. In contrast, alkalinity is ionotropic. Myocardial ischemia, in both adults and infants, should be prevented and treated by alkaline perfusion cooling and by frequent coronary perfusion of a cardiopreservative solution which is extremely cold (4 to 8 degrees C.), oxygenated, has a pH of 7.8, slightly hyperosmolar and which has a hematocrit of 20 per cent (imidazole, erythrocytes and plasma protein colloid), a cardioplegic ionic pattern and energy substrates. Reperfusion of the heart should begin at a 37 pH of 7.8. Evidence is strong that the use of CO2 added to any gas mixture is harmful. It increases myocardial acidosis; it does not increase cerebral blood flow during hypothermia. Protection of the unperfused brain of an infant should emphasize prevention of circulatory arrest prolonged to more than 40 minutes. Temporary reperfusion at that time limit should be used. Probably the best general management of the body for H-CPB is alpha-stat, which preserves biologic neutrality. The uncorrected analyzer reads pH 7.4 and Pco2 at any temperature. However, the need for preservation of the hypoxic heart is overwhelming and, thus, the best acid-base management for cardiac hypothermic operations is significant respiratory alkalosis. The most appropriate sites for the collection of blood samples for gas analysis and measuring temperatures were discussed; "body temperature" is the most unreliable parameter measured. The major characteristics of an "ideal" cardiopreservative solution were described.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The importance of acid-base management for cardiac and cerebral preservation during open heart operations. 642 51

In a previous study we showed that hypothermia of 30 degrees C can expand the time during which retinal neurons in vitro can have their metabolism inhibited without adverse effects. In isolated chick retinae, the first signs of acute toxicity resulting from mild, partial, pharmacological inhibition of metabolism are N-methyl-D-aspartate (NMDA)-mediated histological swelling and gamma-aminobutyric acid release. More prolonged or severe inhibition of metabolism results in involvement of non-NMDA glutamate receptors and voltage-dependent Na+ channels. In this study we examine early cellular events that may be associated with hypothermic protection. The early cellular events thought to follow metabolic stress involve a decrease in ATP, reduced activity of the Na+, K(+)-ATPase, which renders ion leakage unopposed, degradation of the membrane potential and subsequent activation of ionotropic glutamate receptors and voltage-dependent Na+ channels, which leads to acute toxicity. Reduction by hypothermia of the rate of loss of ATP was shown, In past work, to only partially account for neuroprotection. In the present study, inhibition of the Na+, K(+)-ATPase with 10 microM ouabain for 30 min at 37 degrees C led to acute toxicity that was similar to the toxicity produced by severe metabolic stress, i.e., primarily excitotoxic and mediated by NMDA receptors and secondarily involving non-NMDA receptors and voltage-dependent Na+ channels. Swelling and increased gamma-aminobutyric acid release were first evident at 15 min of incubation with ouabain at 37 degrees C. Hypothermia (30 degrees C) delayed the onset of acute excitotoxicity caused by ouabain. This protection was independent of an involvement with ATP loss, because ouabain treatment did not reduce ATP levels. Protection against ouabain suggests that hypothermia can intervene at steps subsequent to decreased Na+, K(+)-ATPase activity. In contrast, reducing the temperature to 30 degrees C did not attenuate NMDA-mediated secondary excitotoxicity caused by lowering of the membrane potential with increasing extracellular K+ concentrations (32-55 mM). However, hypothermia of 30 degrees C was able to reduce the rate of ouabain-induced 86Rb efflux. The findings described above suggest that a critical site of action for hypothermic protection is at a step between decreased Na+, K(+)-ATPase activity and degraded membrane potential, specifically, slowing of the rate of ion leakage.
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PMID:Hypothermia and metabolic stress: narrowing the cellular site of early neuroprotection. 885 11

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

Human NTera2 teratocarcinoma cells were differentiated into postmitotic NT2-N neurons and exposed to hypoxia for 6 h. The cultures were evaluated microscopically, and percent lactate dehydrogenase (LDH) release after 24 and 48 h was used as an assay for cell death. After 48 h LDH release was 24.3 +/- 5.6% versus 13.8 +/- 3.7% in controls (p < 0.001). Cell death was greatly diminished by MK-801 pretreatment (15.4 +/- 5.1%, p < 0.001). If glutamine was omitted from the medium, glutamate levels after 6 h of hypoxia were reduced from 101 +/- 63 to 2.3 +/- 0.3 microM, and cell death at 48 h was also markedly reduced (15.4 +/- 4.5%, p < 0.001). The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (18.7 +/- 5.1%, p < 0.001) and mild hypothermia (33.5-34 degrees C) during hypoxia (19.5 +/- 2.7%, p < 0.05) were moderately protective. Basic fibroblast growth factor (24.1 +/- 3.2%), the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (22.8 +/- 8.1%), the antioxidant N-tert-butyl-o-phenyinitrone (18.9 +/- 5.9%), and the 21-aminosteroid U74389G (24.0 +/- 3.4%) did not protect the cells. N-Acetyl-L-cysteine even tended to increase cell death (30.1 +/- 2.5%, p = 0.06). Treatment with MK-801 at the end of hypoxia did not reduce cell death (23.3 +/- 2.3%). In separate experiments, a 15-min exposure to 1 mM glutamate without hypoxia did not result in significant cell death (14.7 +/- 2.4 vs. 12.2 +/- 2.1%, p = 0.07). We conclude that, although somewhat resistant to glutamate toxicity when normoxic, NT2-N neurons die via an ionotropic glutamate receptor-mediated mechanism when exposed to hypoxia in the presence of glutamate. As far as we know, this is the first reported analysis of the mechanism of hypoxic cell death in cultured human neuronlike cells.
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PMID:Hypoxic cell death in human NT2-N neurons: involvement of NMDA and non-NMDA glutamate receptors. 975 Nov 88

Glutapyrone, a disodium salt of 2-(2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine-4-carboxamido)- glutaric acid, is a representative of a novel 'class' of amino acid-containing 1,4-dihydropyridine (DHP) compounds developed at the Latvian Institute of Organic Synthesis, Riga, Latvia. Conceptually, the glutapyrone molecule can be regarded as a dipeptide-mimicking structure formed by the "free" amino acid (glutamate) moiety and "crypto" (built into the DHP cycle) amino acid ("GABA") elements. Both of these amino acids are joined by the peptide bond. This compound unlike classical DHPs lacks calcium antagonistic or agonistic properties. Our previous studies revealed a profound and long-term anticonvulsant, stress-protective and neurodeficit-preventive activities of glutapyrone. In view of structural properties the role of glutamatergic mechanisms in the mediation of central effects of glutapyrone was considered. In the present study glutapyrone at the concentration range of 1 microM(-1) mM failed to effect both NMDA ([3H]TCP) and non-NMDA ([3H]KA and [3H]AMPA) receptor ligand binding in the rat cortical membranes in vitro. The compound markedly enhanced motor hyperactivity induced by the NMDA antagonist PCP and the dopamine releasing compound D-amphetamine in the rats. Glutapyrone displayed activity in a variety of animal models relevant for affective/depressive disorders in humans i.e. reserpine-induced ptosis and hypothermia, forced swimming test and open field test. These data indicate that the unusually "broad" pharmacological spectrum of glutapyrone might involve concomitant actions on multiple neurotransmitter systems, particularly, GABA-ergic and the catecholamines. It is discussed whether these functional properties are secondary to action on intracellular events, predominantly, G protein-related since glutapyrone appears to lack direct interactions with a number of receptors including ionotropic glutamate and GABA(A)/Bzd receptors.
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PMID:"Atypical" neuromodulatory profile of glutapyrone, a representative of a novel 'class' of amino acid-containing dipeptide-mimicking 1,4-dihydropyridine (DHP) compounds: in vitro and in vivo studies. 992 26

This study characterized the neuroprotective and behavioral effects of (3aS,6aS)-6a-naphtalen-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c]furan-1-on (BAY 36-7620), a novel, selective and systemically active metabotropic glutamate (mGlu)(1) receptor antagonist. In the rat, neuroprotective effects were obtained in the acute subdural hematoma model (efficacy of 40-50% at 0.01 and 0.03 mg/kg/h, i.v. infusion during the 4 h following surgery); whereas in the middle cerebral artery occlusion model, a trend for a neuroprotective effect was obtained after triple i.v. bolus application of 0.03-3 mg/kg, given immediately, 2 and 4 h after occlusion. Hypothermic effects were mild and only obtained at doses which were considerably higher than those at which maximal neuroprotective efficacy was obtained, indicating that the neuroprotective effects are not a consequence of hypothermia. BAY 36-7620 protected against pentylenetetrazole-induced convulsions in the mouse (MED: 10 mg/kg, i.v.). As assessed in rats, BAY 36-7620 was devoid of the typical side-effects of the ionotropic glutamate (iGlu) receptor antagonists phencyclidine and (+)-5-methyl-10,11-dihydroxy-5H-dibenzo(a,d)cyclohepten-5,10-imine (MK-801). Thus, BAY 36-7620 did not disrupt sensorimotor gating, induce phencyclidine-like discriminative effects or stereotypical behavior, or facilitate intracranial self-stimulation behavior. Although behavioral stereotypies and disruption of sensorimotor gating induced by amphetamine or apomorphine were not affected by BAY 36-7620, the compound attenuated some behavioral effects of iGlu receptor antagonists, such as excessive grooming or licking, and their facilitation of intracranial self-stimulation behavior. It is concluded that mGlu(1) receptor antagonism results in neuroprotective and anticonvulsive effects in the absence of the typical side-effects resulting from antagonism of iGlu receptors.
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PMID:Neuroprotective and behavioral effects of the selective metabotropic glutamate mGlu(1) receptor antagonist BAY 36-7620. 1167 37

It has been reported that systemic injection of arginine vasopressin (AVP) induces a drop in body core temperature (T(c)), but little is known about the mechanisms involved. Because glutamate is an important excitatory neurotransmitter involved in a number of thermoregulatory actions, in the present study, we tested the hypothesis that glutamate plays a role in systemic AVP-induced hypothermia. Wistar rats were pretreated intracerebroventricularly (icv) with kynurenic acid, an antagonist of l-glutamate ionotropic receptors, alpha-methyl-(4-carboxyphenyl)glycine (MCPG), an antagonist of l-glutamate metabotropic receptors, or saline 15 min before intravenous injection of AVP (2 microg/kg) or saline. T(c), brown adipose tissue (BAT) temperature, blood pressure, heart rate, and tail skin temperature were measured continuously. Administration of saline icv followed by intravenous AVP caused a significant drop in T(c) brought about by a reduction in BAT thermogenesis and an increase in heat loss through the tail. MCPG treatment (icv) did not affect the fall in T(c) induced by AVP. Treatment with kynurenic acid (icv) abolished AVP-induced hypothermia but did not affect the AVP-evoked rise in blood pressure or drop in heart rate and BAT temperature. Heat loss through the tail was significantly reduced in animals injected with AVP and pretrated with kynurenic acid. These data indicate that ionotropic receptors of l-glutamate in the central nervous system participate in peripheral AVP-induced hypothermia by affecting heat loss through the tail.
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PMID:Role of L-glutamate in systemic AVP-induced hypothermia. 1239 Oct 90

Rostral ventrolateral medulla (RVLM) is a region in the brainstem that is involved in the physiologic responses to hypoxia (i.e. hyperventilation and regulated hypothermia) and contains l-glutamate receptors. Therefore, we examined the effects of blocked of glutamatergic receptors in the RVLM on hypoxic hyperventilation and regulated hypothermia. Ventilation (V(E)) and body temperature (T(b)) were measured before and after bilaterally microinjection of kynurenic acid (KYN, 5 nmol/100 nl, an ionotropic glutamatergic receptors antagonist) and alpha-methyl-4-carboxyphenylglycine (MCPG, 10 nmol/100 nl, a metabotropic glutamatergic receptors antagonist) into the RVLM, followed by a 60-min period of hypoxia exposure. Control rats received microinjection of saline (vehicle). KYN or MCPG into the RVLM did not change V(E) and T(b) under normoxia, but reduced the hypoxic hyperventilation due to a lower tidal volume, although regulated hypothermia persisted. These data suggest that glutamatergic receptors in the RVLM are involved in the ventilatory response to hypoxia, exercising an excitatory modulation of the RVLM neurons, but play no role in hypoxia-induced hypothermia.
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PMID:Glutamatergic receptors of the rostral ventrolateral medulla are involved in the ventilatory response to hypoxia. 1576 1

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

Cerebral palsy (CP) is a group of disorders of movement and posture resulting from nonprogressive disturbances of the fetal or neonatal brain. More than 80% of cases of CP in term infants originate in the prenatal period; in premature infants, both prenatal or postnatal causes contribute. The most prevalent pathological lesion seen in CP is periventricular white matter injury (PWMI) resulting from vulnerability of the immature oligodendrocytes (pre-OLs) before 32 wk of gestation. PWMI is responsible for the spastic diplegia form of CP and a spectrum of cognitive and behavioral disorders. Oxidative stress and excitotoxicity resulting from excessive stimulation of ionotropic glutamate receptors on preOLs are the most prominent molecular mechanisms for PWMI. Asphyxia around the time of birth in term infants accounts for less than 15% of CP in developed countries but the incidence is higher in underdeveloped areas. Asphyxia causes a different pattern of brain injury and CP than is seen after preterm injuries. This type of CP is associated with the clinical syndrome of hypoxic-ischemic encephalopathy shortly after the insult, and the cortex, basal ganglia, and brainstem are selectively vulnerable to injury. Experimental models indicate that neurons in the neonatal brain are more likely to die by delayed apoptosis extending over days to weeks than those in the adult brain. Neurons die by glutamate-mediated excitotoxicity involving downstream caspase-dependent and caspase-independent cell death pathways. Recent reports indicate that males and females preferentially utilize different pathways. Clinical trials indicate that mild hypothermia reduces death or disability in term infants following asphyxia and basic research suggests that this approach might be combined with pharmacological strategies in the future.
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PMID:Cerebral palsy. 1702 68


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