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

Perinatal brain damage in the mature fetus is usually brought about by severe intrauterine asphyxia following an acute reduction of the uterine or umbilical circulation. The areas most heavily affected are the parasagittal region of the cerebral cortex and the basal ganglia. The fetus reacts to a severe lack of oxygen with activation of the sympathetic-adrenergic nervous system and a redistribution of cardiac output in favor of the central organs (brain, heart and adrenals). If the asphyxic insult persists, the fetus is unable to maintain circulatory centralization, and the cardiac output and extent of cerebral perfusion fall. Owing to the acute reduction in oxygen supply, oxidative phosphorylation in the brain comes to a standstill. The Na+/K+ pump at the cell membrane has no more energy to maintain the ionic gradients. In the absence of a membrane potential, large amounts of calcium ions flow through the voltage-dependent ion channels, down an extreme extra-/intracellular concentration gradient, into the cell. Current research suggests that the excessive increase in levels of intracellular calcium, so-called calcium overload, leads to cell damage through the activation of proteases, lipases and endonucleases. During ischemia, besides the influx of calcium ions into the cells via voltage-dependent calcium channels, more calcium enters the cells through glutamate-regulated ion channels. Glutamate, an excitatory neurotransmitter, is released from presynaptic vesicles during ischemia following anoxic cell depolarization. The acute lack of cellular energy arising during ischemia induces almost complete inhibition of cerebral protein biosynthesis. Once the ischemic period is over, protein biosynthesis returns to preischemic levels in non-vulnerable regions of the brain, while in more vulnerable areas it remains inhibited. The inhibition of protein synthesis, therefore, appears to be an early indicator of subsequent neuronal cell death. A second wave of neuronal cell damage occurs during the reperfusion phase. This cell damage is thought to be caused by the postischemic release of oxygen radicals, synthesis of nitric oxide (NO), inflammatory reactions and an imbalance between the excitatory and inhibitory neurotransmitter systems. Part of the secondary neuronal cell damage may be caused by induction of a kind of cellular suicide programme known as apoptosis. Interestingly, there is increasing evidence from recent clinical studies that perinatal brain damage is closely associated with ascending intrauterine infection before or during birth. However, a major part of this damage is likely to be of hypoxic-ischemic nature due to LPS-induced effects on fetal cerebral circulation. Knowledge of these pathophysiological mechanisms has enabled scientists to develop new therapeutic strategies with successful results in animal experiments. The potential of such therapies is discussed here, particularly the promising effects of intravenous administration of magnesium or postischemic induction of cerebral hypothermia.
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PMID:Perinatal brain injury. 1123 23

Brain injury due to bacterial meningitis results in a high mortality rate and significant neurologic sequelae in survivors. The objective of this study was to determine if the application of moderate hypothermia shortly after the administration of antibiotics would attenuate the inflammatory response and increase in intracranial pressure that occurs in meningitis. For this study we used a rabbit model of severe Group B streptococcal meningitis. The first component of this study evaluated the effects of hypothermia on blood-brain barrier function and markers of inflammation in meningitic animals. The second part of the study evaluated the effects of hypothermia on intracranial pressure, cerebral perfusion pressure and brain edema. This study demonstrates that the use of hypothermia preserves CSF/serum glucose ratio, decreases CSF protein and nitric oxide and attenuates myeloperoxidase activity in brain tissue. In the second part of this study we show a decrease in intracranial pressure, an improvement in cerebral perfusion pressure and a decrease in cerebral edema in hypothermic meningitic animals. We conclude that in the treatment of severe bacterial meningitis, the application of moderate hypothermia initiated shortly after antibiotic therapy improves short-term physiologic measures associated with brain injury.
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PMID:Hypothermia as an adjunctive treatment for severe bacterial meningitis. 1103 98

This study examined the ability of the anti-opioid Neuropeptide FF (NPFF) to modify the endogenous activity of nitric oxide (NO). Antinociceptive and hypothermic effects of 1DMe (D.Tyr-Leu-(n.Me)Phe-Gln-Pro-Gln-Arg-Phe-NH(2)), an NPFF agonist, and of L-NAME (N(omega)nitro-L-arginine methyl ester), an inhibitor of nitric oxide synthase, were investigated in mice. Intraperitoneal (i.p.) injection of L-NAME induced, in the hot plate test, a dose-dependent antinociception not reversed by naloxone, an opioid antagonist, but inhibited by L-Arg, the NO synthesis precursor. Intracerebroventricular (i.c.v.) injections of 1DMe inhibit the antinociceptive activity of L-NAME in a dose-dependent manner. On the contrary, L-NAME markedly potentiated hypothermia induced by 1DMe injected in the third ventricle. These data show that Neuropeptide FF receptors exert a dual effect on endogenous NO functions and could modulate pain transmission independently of opioids.
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PMID:Opposing interplay between Neuropeptide FF and nitric oxide in antinociception and hypothermia. 1103 7

Hypothermic cardiopulmonary bypass alters platelet function and hypothermia is associated with postoperative myocardial ischemia. Thrombogenic surfaces such as extracorporeal circuits, vascular graft materials, and components of atherosclerotic plaque induce activation of platelets. The effects of human hemoglobin (Hb) covalently modified to carry S-nitric oxide (NO) functional groups (SNO-Hb), polyethylene glycol (PEG-Hb), and SNO-PEG-Hb on platelet activation were studied. Platelet activation was assessed by cytometric analysis of GPIIb-IIIa activation and P-selectin expression at hypothermic condition (22 degrees C) after stimulation with Hb derivatives. Platelet adhesion and aggregation were measured in a parallel glass plate chamber coated with unmodified Hb, SNO-Hb, PEG-Hb, SNO-PEG-Hb, and collagen. Platelet binding of antibodies to GPIIb-IIIa and P-selectin was significantly enhanced by hypothermic condition and by unmodified Hb. There was significantly less platelet binding of antibodies to GPIIb-IIIa and P-selectin with SNO-Hb, PEG-Hb, and SNO-PEG-Hb compared with unmodified Hb. There was significantly less platelet attachment, adhesion, and aggregation on the SNO-Hb, PEG-Hb and SNO-PEG-Hb coated surfaces compared with unmodified Hb-coated and -uncoated surfaces. SNO-Hb, PEG-Hb, and SNO-PEG-Hb induced less platelet activation at hypothermic temperature, and induced less platelet adhesion and aggregation on thrombogenic surfaces compared with unmodified Hb. The inhibitory effect may be derived from antiadhesive properties of Hb, antiplatelet actions of NO, and molecular barrier action of PEG.
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PMID:Attenuation of hypothermia-induced platelet activation and platelet adhesion to artificial surfaces in vitro by modification of hemoglobin to carry S-nitric oxide and polyethylene glycol. 1115 32

Septic shock, a major cause of death, is characterized by a pathophysiologic increased production of nitric oxide (NO), which leads to vasodilation and myocardial toxicity. Septic Escherichia coli frequently express proteinaceous curli fibers. In this study, curliated E. coli induced high levels of NO by directly inducing type 2 nitric oxide synthase (NOS2) both in vitro and in vivo. More severe hypotension and higher plasma nitrite/nitrate levels were seen in wild type mice systemically infected with curliated E. coli than in animals infected with E. coli mutants that lacked curli proteins. Blood pressure remained stable in NOS2-deficient mice with curliated bacteria. Increased heart rates, transient hypothermia, and loss of gross activity were seen in all mice, regardless of curli expression. Study results suggest that expression of curli fibers by E. coli activates the NO/NOS2 arm of the innate immune system, which leads to a significant fall in blood pressure.
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PMID:Activation of inducible nitric oxide synthase/nitric oxide by curli fibers leads to a fall in blood pressure during systemic Escherichia coli infection in mice. 1117 Sep 87

Cerebral arteries are innervated by nitric oxide (NO)-mediated vasodilator nerves, and hypoxia has been shown to attenuate neurogenic vasorelaxation. The present study examines the effects of hypothermia on neurogenic vasorelaxation and on the hypoxia-induced inhibition of the neurogenic vasorelaxation response. In isolated canine cerebral arteries, relaxant responses to transmural electrical stimulation (5 Hz for 40 s), mediated via NO synthesized from L-arginine, were not influenced by lowering the bathing media temperature from 37 degrees C to 30 degrees C but were attenuated at 25 degrees C. On the other hand, relaxations caused by nicotine and exogenous NO were not significantly attenuated but were prolonged by cooling to 25 degrees C. The responses associated with nerve stimulation by electrical pulses or nicotine were depressed by hypoxia (from about 500 mmHg of partial O2 pressure to about 45 mmHg) under normothermia. However, hypothermia at 25 degrees C prevented the inhibition by hypoxia of the neurogenic relaxation. It is concluded that the hypothermia-induced inhibition in the response to electrical nerve stimulation is not associated with a decreased synthesis and release of NO in vasodilator nerves nor with a reduced ability of smooth muscle to relax in response to NO. Interference with the propagation of action potentials might be involved in the inhibition via a fall of temperature. The fact that the hypoxia-induced impairment of vasodilator nerve function was prevented by cooling may partially explain the efficacy of hypothermia in protecting against ischemic neuronal injury in the brain.
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PMID:Hypothermia on NO-mediated neurogenic relaxation and on hypoxic inhibition in the response of canine cerebral arteries. 1121 30

Hypothermia is a well-known phenomenon which accompanies hypoglycemia in mammals. The present study was designed to test the hypothesis that nitric oxide (NO) plays a role in insulin-induced hypothermia. The body temperature (Tb) of awake, unrestrained rats was measured before and after systemic infusion of insulin (2U x kg(-1) x h(-1)), and intracerebroventricular administration of NG-nitro-(L)-arginine methyl ester (L-NAME, a nonselective NO synthase inhibitor, 200 microg/1 microl). We observed a significant reduction in body temperature after insulin infusion. L-NAME alone caused no significant change in body temperature. When the two treatments were combined, no change in Tb was observed. The data indicate that NO plays a key role in insulin-induced hypothermia.
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PMID:Role of nitric oxide in insulin-induced hypothermia in rats. 1122 13

Increases in extracellular glutamate during cerebral ischemia may play an important role in neuronal injury. Lubeluzole is a novel neuroprotective drug, which in previous in vitro and focal ischemia studies has been shown to inhibit nitric oxide synthesis, to block voltage-gated Na+-ion channels, and to inhibit glutamate release. In this study, we investigated the ability of lubeluzole to inhibit glutamate accumulation during episodes of transient global cerebral ischemia. Twenty-five New Zealand white rabbits were randomized to one of four groups: a normothermic control group; a hypothermic group; a 1.25 mg/kg lubeluzole group; or a 2.5 mg/kg lubeluzole group. The animals were anesthetized, intubated, and ventilated before microdialysis probes were placed in the hippocampus. Lubeluzole was given intravenously 90 min before the onset of ischemia. Esophageal temperature was maintained at 38 degrees C in the control, and lubeluzole treated groups, while the animals in the hypothermia group were cooled to 30 degrees C. A 15-min period of global cerebral ischemia was produced by inflating a neck tourniquet. Glutamate concentrations in the microdialysate were determined using high-performance liquid chromatography (HPLC). During ischemia and early reperfusion, glutamate concentrations increased significantly in the control group and returned to baseline after 15 min of reperfusion. In the lubleuzole 2.5 mg/kg and hypothermia groups, glutamate levels were significantly lower (P<0.05) than in the control group and there was no significant change from baseline levels during the entire experiment. This study suggests that lubeluzole is effective in inhibiting extracellular glutamate accumulation during global cerebral ischemia, and has the potential to produce potent neuroprotection when instituted prior to an ischemic event.
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PMID:Lubeluzole inhibits accumulation of extracellular glutamate in the hippocampus during transient global cerebral ischemia. 1130 16

The delayed preconditioning of the heart by monophosphoryl lipid A is mediated by endogenous nitric oxide (NO), and the cardioprotection afforded by nitroglycerin is related to stimulation of calcitonin gene-related peptide (CGRP) release. The objective of this study was to explore whether improvement of preservation with cardioplegia by monophosphoryl lipid A is mediated by CGRP. In addition, we examined the effect of monophosphoryl lipid A on the tumor necrosis factor-alpha (TNF-alpha) content of myocardial tissues. The isolated rat heart was perfused in the Langendorff mode. Heart rate, coronary flow, left-ventricular pressure, and its first derivatives (+/-dp/dt(max)) were recorded, and plasma levels of NO and CGRP, the release of creatine kinase in coronary effluent and the content of TNF-alpha in myocardial tissues were measured. Hypothermic ischemia for 4 h caused a decline in cardiac function, and an increase in the release of creatine kinase and in the content of TNF-alpha. Pretreatment with monophosphoryl lipid A (500 microg/kg, i.p.) for 24 h improved the recovery of cardiac function and reduced the release of creatine kinase concomitantly with a decrease in the content of cardiac TNF-alpha. Monophosphoryl lipid A markedly increased plasma concentrations of CGRP and NO. After pretreatment with L-nitroarginine methyl ester (L-NAME), the cardioprotection and the increased release of NO and CGRP induced by monophosphoryl lipid A were abolished. Capsaicin also abolished the cardioprotection and the increased release of CGRP induced by monophosphoryl lipid A, but did not affect the content of NO. The results suggest that monophosphoryl lipid A-induced preconditioning enhances preservation with cardioplegia and that the protective effects of monophosphoryl lipid A are related to stimulation of CGRP release.
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PMID:Monophosphoryl lipid A-induced delayed preconditioning is mediated by calcitonin gene-related peptide. 1140 36

Oxidative stress is one of the major causes of cellular injury. Various reactive oxygen (ROS) and nitrogen (RNS) species such as superoxide, hydroxyl radical, peroxynitrite, and nitric oxide are involved in the manifestations of different types of organ toxicity and the resultant syndromes, symptoms, or diseases. Hypothermic conditions have been reported to reduce the oxidative stress in various in vitro and in vivo studies. In the present study, we sought to determine the effect of lowered temperatures on oxidative stress-induced cell death in Chinese hamster ovary (CHO) cells. We also investigated the oxidative stress-induced alterations in the expression of anti-apoptotic protein, bcl-2, in CHO cells at lowered temperatures. CHO cells were incubated at four different temperatures of 30, 32, 35, and 37 degrees C (control temperature) from 1 to 4 d. In another set, the cells were incubated with 100 microM hydrogen peroxide (H(2)O(2)) for 30 min before harvesting at different time points. The cells were harvested at 1, 2, 3, and 4 d. Cell survival was significantly higher at 30 degrees C as compared to 37 degrees C over 4 d of incubation. In cells incubated with H(2)O(2), significantly higher cell viability was observed at lower temperatures as compared to the cells incubated at 37 degrees C. The activity of glutathione peroxidase (GSH-Px) also increased significantly at lower temperatures. Lowered temperature also provided a significant increase in the expression of anti-apoptotic protein, bcl-2 after 4 d of incubation. These data suggest that hypothermic conditions lowers the risk of oxidative stress-induced cellular damage and programmed cell death by increasing the activity of GSH-Px and by the induction in the expression of the anti-apoptotic protein, bcl-2.
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PMID:Hypothermia enhances bcl-2 expression and protects against oxidative stress-induced cell death in Chinese hamster ovary cells. 1146 79


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