Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To record brain temperature for comparison with rectal and temporalis muscle temperatures in preliminary studies before MR spectroscopy experiments, a thermistor was inserted into the basal ganglia in eight anesthetized, ventilated, and physiologically monitored rats. The rats were placed in an MR spectrometer and subjected to 60 min of global cerebral ischemia and 2 h of reperfusion without radiofrequency (RF) pulsing. Body temperature was maintained at 37.5-38.0 degrees C (normothermia) or 36.5-37.0 degrees C (mild hypothermia). Brain temperature during ischemia, which dropped to 31.9 +/- 0.3 (hypothermia) and 33.6 +/- 0.5 degrees C (normothermia), correlated with temporalis muscle temperature (r2 = 0.92) but not with body or magnet bore temperature measurements. Ischemia reduced brain temperature approximately 1.7 degrees C in rats subjected to mild hypothermia (1 degree reduction of body temperature). Parallel MR spectroscopy experiments showed no significant difference in energy metabolites between normothermic and hypothermic rats during ischemia. However, the metabolic recovery was more extensive 20-60 min after the onset of reperfusion in hypothermic rats, although not thereafter (P < 0.05). Mild hypothermia speeds metabolic recovery temporarily during reperfusion but does not retard energy failure during global ischemia in rats.
 ...
PMID:Effect of brain, body, and magnet bore temperatures on energy metabolism during global cerebral ischemia and reperfusion monitored by magnetic resonance spectroscopy in rats. 917 33

We investigated the protective effect of hypothermia on ultra-early-type ischemic injury in the thalamic reticular nucleus of the rat. Cerebral ischemia was produced by 5 min of cardiac arrest followed by resuscitation. Rectal and cranial temperature during and after cardiac arrest was maintained at 37-38 degrees C in the normothermic group and at 32-33 degrees C in the hypothermic group. In the postischemic hypothermic group, temperature was maintained at 32-33 degrees C starting 15 min after normothermic ischemia. Histological damage was evaluated quantitatively. While after 5 min of recirculation there was no difference in morphological changes in terms of neuronal halo formation, intraischemic hypothermia reduced the severity of the degenerative changes represented by vacuolated or dark neurons by 15 min. Postischemic hypothermia failed to show any evidence of protection by 30 min. The protective effect of intraischemic hypothermia remained significant when evaluated at 14 days after ischemia by volumetry of the lesion and neuronal density analysis, whereas postischemic hypothermia had no clear protective effect. These results suggest that the protective effect of intraischemic hypothermia applies to neurons susceptible to ultra-early-type injury, but the effect of postischemic hypothermia is limited because normothermic ischemia results in extensive degeneration in these neurons by 15 min.
 ...
PMID:Limited but significant protective effect of hypothermia on ultra-early-type ischemic neuronal injury in the thalamus. 918 92

Hypothermia protects the brain and other vital organs during periods of ischaemia. We differentiate between mild (36-34 degrees C), moderate (33-29 degrees C), deep (28-17 degrees C) and profund (16-4 degrees C) hypothermia. During hypothermia, cerebral metabolic rate and cerebral blood flow decrease dependent on temperature. The relation between temperature and cerebral metabolism is expressed by the temperature coeffizient Q10, which is the ratio between two metabolic rates separated by 10 degrees C. The following factors contribute to decreases in cerebral blood flow seen during hypothermia: cerebral metabolic depression, decreases in cardiac output, and decreases in arterial blood pressure with pH-stat management, increases in hematocrit and in blood viscosity. Mild or moderate hypothermia reduces histopathological damage and neurological deficits if started before and during cerebral ischaemia. Hypothermia may also improve neurologic outcome if initiated following focal cerebral ischaemia, but is less effective after global ischaemic insults. Mild hypothermia appears to be safer and more effective compared to moderate hypothermia. In most instances, deep hypothermia renders neurologic outcome worse, which is most likely related to the generation of toxic metabolites and inadequate myocardial function during rewarming. The neuroprotective effects of hypothermia are related to several mechanisms along the ischaemic cascade: prevention of postischaemic hypoperfusion, reduction of functional and basal metabolism, decreased accumulation of lactic acid and oedema formation, inhibition of excitatory neurotransmitter release, prevention of Ca(++)- and Na(+)-influx, inhibition of lipid peroxidase activity, and free radical formation, stimulation of regenerative immediate early genes. The side effects of hypothermia include myocardial ischaemia, cardiac arrhythmias, decreased left ventricular contractility, coagulation abnormalities, and suppression of metabolic and immunological processes.
 ...
PMID:[Mild and moderate hypothermia as a new therapy concept in treatment of cerebral ischemia and craniocerebral trauma. Pathophysiologic principles]. 928 20

PNU-101017 is a novel, imidazoquinoline amide and benzodiazepine receptor partial agonist that has high affinity for the GABAA receptor subtypes containing the alpha 1 and alpha 3 or alpha 5 subunits. At each of these receptors, the compound is a partial agonist with approximately 50% of the intrinsic activity of the full agonist diazepam. In view of the previously demonstrated anti-ischemic effects of some GABA agonists, the purpose of this study was to determine the ability of PNU-101017 to salvage selectively vulnerable neuronal populations in the gerbil forebrain ischemia model. In an initial set of experiments, male gerbils were pretreated 30 minutes before ischemia induction (5 minutes) with PNU-101017 (3, 10, or 30 mg/kg intraperitoneally) and again 2 hours after reperfusion. In vehicle (0.05 N HC1)-treated gerbils, the loss of hippocampal CA1 neurons at 5 days was 80%. PNU-101017 was shown to produce a dose-related increase in CA1 neuronal survival; at either 10 or 30 mg/kg, the loss of CA1 neurons was only 21% (P < 0.005 versus vehicle). A second experiment, examined the therapeutic window for PNU-101017 using the dose level of 30 mg/kg intraperitoneally. Administration of the first of two doses (2 hours apart) at the time of reperfusion resulted in an identical decrease in CA1 damage at 5 days to that seen with preischemic treatment (P < 0.003 versus vehicle). Even with a delay of the initial dosing until 4 hours after reperfusion, PNU-101017 reduced CA1 neuronal loss to only 32% (P < 0.01 versus vehicle). In a third experiment in which the duration of the ischemic insult was increased to 10 minutes and the brains were not analyzed until 28 days after ischemia, daily PNU-101017 dosing for the full 28 days still significantly preserved CA1 neurons, although less effectively than in the milder 5 minute-ischemia model. The loss of dopaminergic nigrostriatal neurons was also reduced. The neuroprotective effect of PNU-101017 was not associated with any overt CNS depression and it did not correlate with hypothermia. This benzodiazepine-receptor partial agonist may have potential for the treatment of global cerebral ischemia.
 ...
PMID:Neuroprotective properties of the benzodiazepine receptor, partial agonist PNU-101017 in the gerbil forebrain ischemia model. 929 May 85

A retrospective, nonrandomized study of blood glucose levels in very young children under 6 kg was undertaken. Each patient underwent the repair of complex congenital heart defects using hypothermia and nonpulsatile cardiopulmonary bypass (CPB). Hyperglycaemia may cause metabolic changes, resulting in reduced glucose transport and cerebral ischaemia. To evaluate the frequency of the occurrence of hyperglycaemia, samples were evaluated for glucose levels in three groups of patients. Group 1 (n = 5) consisted of infants undergoing standard bypass and moderate hypothermia (26 degrees C). Group 2 (n = 5) were infants undergoing low-flow bypass and profound hypothermia (20 degrees C). Group 3 (n = 5) was comprised of infants undergoing total circulatory arrest and profound hypothermia (18 degrees C). Glucose samples were taken preoperatively, during hypothermic bypass, during rewarming and 1-h postoperatively. In group 1, blood glucose levels remained within the normal range (65-100 mg/dl) throughout bypass and in the 1-h postoperative sample. In group 2, blood glucose levels remained within the normal range preoperatively and during the hypothermic bypass period. However, during the rewarming period, the glucose level rose to 185 +/- 17.2 mg/dl. The 1-h postoperative level was also increased to 168 +/- 16.5 mg/dl. Group 3, like group 2, showed that the preoperative and hypothermic glucose values were within the normal range and the rewarming, 133 +/- 29.4, and the 1 h, 130 +/- 33.3 mg/dl, glucose values were hyperglycaemic. This study indicates that blood glucose levels should be monitored routinely, both during and after CPB.
 ...
PMID:Glucose management in the infant under six kilograms. 930 Apr 75

Agonists of the GABA-A receptor are neuroprotective after experimental stroke, but studies of GABA-B agonists have contradicted each other. To further investigate whether GABA-B agonists may be neuroprotective, we devised a quantal bioassay using the intraluminal occlusion method of inducing reversible cerebral ischemia. Subjects underwent middle cerebral artery occlusion for varying amounts of time, ranging from 5 to 90 min. Behavioral outcome was measured 48 h later with a quantal observational scale: score of abnormal given for any one of asymmetric forepaw flexion on tail lift, asymmetric grip, circling, reduced exploration, seizures, or death. To the grouped response data the logistic equation was used to find the ED50, the duration of occlusion that caused one-half of the subjects to be abnormal. To find the potency ratio for each drug, we divided the ED50 for treatment by that for vehicle. We administered baclofen, a GABA-B agonist, intraperitoneally 5 min after the onset ofischemia. Baclofen (20 mg/kg) was neuroprotective (potency ratio of 3.0, P < 0.05), but a lower dose (10 mg/kg) was not. However, both doses of baclofen caused significantly more intracerebral hemorrhages than control. In awake animals, both baclofen doses caused significant increases in mean arterial pressure, but no changes in other cardiorespiratory variables. The glutamate antagonist MK-801, the GABA-A agonist muscimol, and hypothermia were all protective using the bioassay (potency ratios ranging from 1.5 to 3.0). We conclude that although baclofen (20 mg/kg) may be neuroprotective, its utility is complicated by postischemic hypertension and cerebral hemorrhages.
 ...
PMID:High dose baclofen is neuroprotective but also causes intracerebral hemorrhage: a quantal bioassay study using the intraluminal suture occlusion method. 934 59

Polyamines and N-methyl-D-aspartate (NMDA) receptors are both thought to play an important role in secondary neuronal injury after cerebral ischemia. Ifenprodil, known as a noncompetitive inhibitor of polyamine sites at the NMDA receptor, was studied after transient focal cerebral ischemia occurred. Spontaneously hypertensive male rats, each weighing between 250 and 350 g, underwent 3 hours of tandem middle cerebral artery (MCA) and common carotid artery occlusion followed by reperfusion for a period of 3 hours or 21 hours. Intravenous ifenprodil (10 microg/kg/minute) or saline infusion was started immediately after the onset of MCA occlusion and continued throughout the ischemic period. Physiological parameters including blood pressure, blood gas levels, blood glucose, hemoglobin, and rectal and temporal muscle temperatures were monitored. Six rats from each group were evaluated at 6 hours postocclusion for brain water content, an indicator of brain edema, and Evans blue dye extravasation for blood-brain barrier breakdown. Infarct volume was also measured in six rats from each group at 6 and 24 hours postocclusion. Ifenprodil treatment significantly reduced brain edema (82.5 +/- 0.4% vs. 83.5 +/- 0.4%, p < 0.05) and infarct volume (132 +/- 14 mm3 vs. 168 +/- 25 mm3, p < 0.05) compared with saline treatment, with no alterations in temporal muscle (brain) or rectal (body) temperature (35.9 +/- 0.4 degrees C vs. 36.2 +/- 0.2 degrees C; 37.7 +/- 0.4 degrees C vs. 37.6 +/- 0.6 degrees C; not significant). These results demonstrate that ifenprodil has neuroprotective properties after ischemia/reperfusion injury in the absence of hypothermia. This indicates that antagonists selective for the polyamine site of the NMDA receptors may be a viable treatment option and helps to explain some of the pathophysiological mechanisms involved in secondary injury after transient focal cerebral ischemia has occurred.
 ...
PMID:Effects of ifenprodil, a polyamine site NMDA receptor antagonist, on reperfusion injury after transient focal cerebral ischemia. 938 5

Currently the most used perfusion techniques during aortic arch surgery to prevent cerebral damage include hypothermic circulatory arrest, retrograde cerebral perfusion and selective cerebral perfusion (SCP). The application of simplified SCP, which does not require deep hypothermia, has become an alternative procedure for brain protection. Including the physiological principle of autoregulated cerebral blood flow, cerebral perfusion flow is not predetermined, but differentiated from the different cannula sizes for the lower and upper body perfusion. In a mock circulation loop, we could show that resistance changes in the two compartments led to flow shifts between the systemic and brachiocephalic regions. In addition to mechanical factors cerebral perfusion is determined from physiological changes. In practice, these shifts can be initiated with disrupted autoregulation due to ph-stat management or dramatic pressure changes. To prevent mismatched cerebral perfusion extended perioperative monitoring was included in our clinical setting. With bilateral somatosensory evoked potentials, a computer aided topographical electroencephalometry system, transcranial doppler-sonography and jugular venous bulb saturation, we could provide a sufficient bihemispheric perfusion. Between 1990 and 1995 we operated on 21 patients using SCP. Intraoperatively no signs of cerebral ischaemia due to inadequate perfusion could be observed. Only temporary neurological changes were found postoperatively. In summary, the simplified SCP, despite its physiological basis, is intricately involved in control and influence. We think that the application of SCP is safe if extended neurophysiological monitoring is included in the clinical setting.
 ...
PMID:Potential problems with simplified selective cerebral perfusion--experimental investigations and clinical improvements. 941 50

In animal stroke models, treatment with mild hypothermia (30-34 degrees C) for 3-4 hours may reduce the size of cerebral infarction if started within three hours of the initiation of cerebral ischaemia. The mechanism by which hypothermia exerts its neuroprotective effect is unknown, but experimental studies have shown the release of neurotoxic excitatory amino acids and free oxygen radicals to be reduced during hypothermic ischaemia. In patients with acute stroke, body temperature above 37.5 degrees C are associated with poor outcome, and temperatures below 36.5 degrees C with improved outcome, compared to normothermic patients. Due to the unpleasantness of cooling and side effects as shivering, hypothermia may not be tolerated by stroke patients without sedation of light anaesthesia which may increase the risk of hypotension and respiratory complications. However, lowering body temperature by 1-2 degrees C may suffice to improve functional outcome in acute stroke patients, and such mild hypothermia should be tested in randomized controlled clinical trials.
 ...
PMID:[Can acute stroke be treated with hypothermia?]. 946 99

The aim of the present study is to compare the influence of timing and duration of mild hypothermia on rats subjected to 3 h of middle cerebral artery occlusion followed by 72 h of reperfusion. Sixty-four Sprague-Dawley rats were divided into three mild hypothermic groups according to the duration of mild hypothermia (MHT 32 +/- 0.2 degrees C): intra-ischemia (MHTi); intra-reperfusion (MHTr); and intra-ischemia/ reperfusion (MHTi + r). Our control group was normothermic (NT 37 +/- 0.2 degrees C). Reversible focal cerebral ischemia was carried out in rats with a suture technique. Cerebral blood flow was measured by laser Doppler flowmetry to confirm occlusion and reperfusion. The permeability of the blood-brain barrier was determined by the extravasation of Evans's blue dye, and infarct volumes were measured by 2,3,5-triphenyltetrazolium chloride staining at 72 h after reperfusion. Acute post-ischemic hyperperfusion and delayed hypoperfusion in the ischemic perifocal area and sustained hypoperfusion in the ischemic core were inhibited in MHTi + r and MHTi rats (p < 0.05) as compared to the NT rats. The action of MHTi + r on preventing post-ischemic progressive hypoperfusion in the perifocal area was more effective than that of MHTi 2 h after reperfusion (p < 0.05). Blood-brain barrier disruption in the basal ganglia and cortex areas was significantly reduced in both MHTi + r and MHTi groups, and especially the former. Infarct volume was significantly reduced in both MHTi and MHTi + r groups (p < 0.05). MHTi and MHTi + r have protective effects for reducing ischemia/reperfusion injury. The potential mechanisms may include inhibition of post-ischemic hyperperfusion, and delayed and sustained hypoperfusion.
 ...
PMID:The effect of extending mild hypothermia on focal cerebral ischemia and reperfusion in the rat. 947 Nov 4


<< Previous 1 2 3 4 5 6 7 8 9 10