Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clinical use of profound hypothermia and total circulatory arrest has been accompanied by occasional postoperative neurological abnormalities. In a series of infant baboons, surface cooling to 32 degrees C (brain) followed by perfusion cooling by cardiopulmonary bypass with a membrane oxygenator and heat exchanger to 18 degrees C was carried out, after which the circulation was stopped for 30 minutes. The animal was rewarmed to 35 degrees C. Marked alterations in the regional cerebral circulation were observed during perfusion cooling and rewarming. Regional cerebral ischemia was negatively correlated with jugular outflow (total cerebral blood flow) during rewarming, while regional hyperemia showed positive correlation both following perfusion cooling and after rewarming. A higher degree of ischemia in brain ischemic samples was found during rewarming than during cooling. These alterations in regional cerebral perfusion were associated with lactacidosis and hyperglycemia after rewarming, and may be considered potentially responsible for posthypothermic cerebral dysfunction.
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PMID:Cerebral effects of profound hypothermia (18 degrees C) and circulatory arrest. 115 33

The effect of nimodipine, a 1,4 dihydro-piridine calcium entry blocker (200 micrograms/kg), was investigated in rats after definitive ischemia or 2 min of global ischemia (neck tourniquet method). The brains were freeze-clamped at the desired time intervals and subjected to high pressure liquid chromatography analyses for nucleotides and enzymatic lactate estimation. Although in the definitive ischemia (removal of the brain) no difference was observed in the treated versus the untreated animals, there was a statistically significant difference in both groups after global ischemia followed by reperfusion. Thirty minutes after reflow the brains of the treated animals contained 1,690 +/- 62 nmol ATP/g as compared to 765 +/- 259 nmol ATP/g in the untreated animals (p less than 0.05). The normal controls amounted to 1,932 +/- 77 nmol ATP/g. Also the adenylate energy charge returned to normal in the treated animals (treated animals and controls 0.69 and 0.72, respectively). From these preliminary data we conclude that nimodipine is able to restore mitochondrial function after ischemia and to maintain a high level of energy-rich phosphates. Thus, calcium entry blockers may be effective in preserving and protecting cerebral tissue from irreversible injury after ischemia.
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PMID:Effect of the calcium entry blocker nimodipine on the metabolism of nucleic acids in rat brain ischemia. 239 9

Numerous experimental studies of blunt spinal cord injury have shown that while a variable degree of immediate mechanical damage occurs to spinal blood vessels and axons in proportion to the magnitude of the injury force, a considerable amount of post-traumatic tissue degeneration is due to a secondary pathophysiological process that may be modifiable by appropriate therapeutic intervention. A growing body of biochemical, physiological, and pharmacological evidence has suggested that oxygen free radical-induced lipid peroxidation, working in concert with aberrant calcium fluxes and eicosanoid generation in particular, plays a key role in progressive post-traumatic spinal cord degeneration. Of particular importance, lipid peroxidation has been linked to microvascular damage and hypoperfusion which, if severe enough, can lead to a secondary ischemic insult to the tissue. The ability of intensive dosing with the glucocorticoid steroid methylprednisolone to beneficially affect post-traumatic ischemia and to promote chronic neurologic recovery in spinal cord injured animals has been correlated not with its glucocorticoid activity, but rather with the ability to inhibit post-traumatic spinal lipid peroxidation. In view of this, a novel series of non-glucocorticoid 21-aminosteroids has been developed which lack glucocorticoid activity but are more effective inhibitors of nervous tissue lipid peroxidation than the glucocorticoid steroids. One of these, U74006F, has now been studied in some detail and appears to be a promising new agent for the acute treatment of spinal cord (and brain) trauma. The background and pre-clinical development of this compound to date is reviewed.
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PMID:New pharmacological treatment of acute spinal cord trauma. 305 17

[1-14C-]Arachidonic acid was injected into the lateral ventricle of the gerbils (meriones unguiculatus) two hours before producing brain ischemia by the bilateral ligation of the carotid arteries. Ten minutes before the carotid ligation a group of animals received an additional intraventricular injection of cold cytidine (2.5 mumol/brain). Control animals with and without cytidine, together with the ischemic group, were decapitated directly into liquid nitrogen ten minutes after carotid ligation or sham surgery. Cytidine is able to both stimulate arachidonic acid incorporation into lipids and noticeably correct the release of this acid from polar lipids induced by ischemia. Based on these findings, it is possible to assume that cytidine exerts an effect on the biosynthesis of phosphoglycerides as well as on their catabolic activities.
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PMID:Effect of cytidine on the modification of phospholipid metabolism induced by ischemia. 310 88

A new method for brain resuscitation following acute focal ischemic insult has been developed in this laboratory. The technique utilizes a surrogate route to supply cerebral metabolites and employs highly oxygenated fluorocarbons (OFNS), which are efficient gas transport and exchange agents, perfused through the ventriculo-subarachnoid spaces. We previously described a return of aerobic metabolism and EEG after severe global ischemia by oxygenated perfusions and now report treatment-induced reduction in the size of experienced cerebral infarction. Twenty-eight cats were anesthetized (choralose and urethane), tracheotomized and placed in a stereotactic frame. Physiologic adjustments assured arterial blood pCO2 28-35 Torr, pO2 100-150 Torr pH 7.4 and glucose less than 200 mg%. The left middle cerebral artery was exposed transorbitally and temporarily clipped along with both common carotids for 2 h. One hour later (3 h after ischemic onset) the treated group were perfused by the ventriculo-cisternal route either with OFNS [pO2 = 600 Torr; 3 ml/min 6 h, 2 ml/min 2 h, 1 ml/min 2 h, 0.5 ml/min 2 h at 10 mm Hg intracranial pressure (ICP)] or with the vehicle perfusate. Eighteen to twenty hours after the ischemic insult the animals were sacrificed. Sections of fresh brain of 0.5 mm thickness were incubated in 1% triphenyl tetrazolium chloride. The infarcted areas were confirmed with classic neuropathologic techniques. Areas of infarction (expressed in cm3 and as % of the brain) were measured using a planimeter. OFNS-treated brains contained 80% less infarcted tissue than the vehicle-perfused or untreated stroked animals. The infarcted areas were significantly treatment reduced (P less than 0.05 ANOVA and Bonferroni tests).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Focal cerebral ischemia: reduction in size of infarcts by ventriculo-subarachnoid perfusion with fluorocarbon emulsion. 315 23

Recent studies on proton NMR imaging revealed its remarkable sensitivity for detecting cerebral ischemia. Since proton NMR reflects the distribution and state of water in the brain, an NMR imager becomes a sensitive in vivo detector of brain edema developing soon after the energy state is compromized by ischemia. To further clarify the usefulness of NMR imaging to characterize the ischemia-induced changes, correlations between T1 and T2 relaxation times and water content of the normal and ischemic rat and gerbil brain were studied by means of both spectroscopic and in vivo imaging methods. In the spectroscopic experiment on excised rat brain (cortex, white matter, hippocampus and thalamus for normal and ischemia-laden brain), T1 and T2 relaxation times and water content were determined. The ischemic insult was induced for 60 min by the method of Pulsinelli followed by 60 min of reperfusion. All of the T1, T2 and water content significantly increased in the ischemic tissue. Gray-white difference was evident in T1 and T1 was linearly correlated with the water content of the tissue. T2 was by far prolonged in the ischemic tissue compared with the increase in the water content, showing greater sensitivity of T2 for detection of ischemia. In the imaging experiment, coronal NMR imaging at 0.5 tesla was performed employing proton density-weighted saturation recovery (TR = 1.6 s, TE = 14 ms), T1-weighted inversion recovery (TR = 1.6 s, TI = 300 ms, TE = 14 ms) and T2-weighted spin echo (TR = 1.6 s, TE = 106 ms) pulse sequences.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Magnetic resonance imaging of experimental cerebral ischemia: correlations between NMR parameters and water content]. 370 79

The mechanisms underlying cardiac standstill in health and disease are considered. Ventricular standstill results from failure of impulse formation or transmission in the ventricles. In the healthy heart, idioventricular automaticity is not brought into play and instead is suppressed by the sinus node by virtue of its faster rate (overdrive suppression). However, should the sinus node activity be suppressed or atrioventricular (AV) conduction blocked, overdrive suppression no longer persists. For this reason, the ventricular pacemakers activate the ventricles at a slow rate and under the regulatory activity of the sympathetic system. In the diseased heart, the idioventricular pacemakers or the regulatory mechanism can be altered structurally or functionally. This can be the result of the disease, compensatory mechanisms or therapeutic interventions. Disease may affect the idioventricular pacemakers directly or indirectly through anoxia, a change in ionic environment or an alteration of sympathetic innervation. Compensatory mechanisms may affect reflex actions, blood supply or heart rate. Drug administration may alter autonomic balance, block the action of neuromediators on their receptors or modify diastolic depolarization or its ability to attain the threshold. Because of these different direct and indirect actions, a sudden cessation of sinus node activity or sudden AV block may result in the diseased heart in a prolonged and even fatal cardiac standstill, especially if the tolerance to ischemia of other organs (notably the brain) is decreased.
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PMID:On the mechanisms underlying cardiac standstill: factors determining success or failure of escape pacemakers in the heart. 388 12

To verify its protective effect on the ischemic mammalian brain, hyperbaric oxygen was administered to six groups of carotid-ligated gerbils. The outcome was evaluated clinically and by a colorimetric videodensitometry technique by comparing differences in the interhemispheric color density through the translucent intact cranium. It was found that there was a graded decrease in interhemispheric differences with increasing exposure to hyperbaric oxygen (the appearance of the ischemic hemisphere increasingly approached that of normal brain). This correlated with the incidence of ischemia in each group.
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PMID:Videodensitometric estimation of the protective effect of hyperbaric oxygen in the ischemic gerbil brain. 401 79

Oxygen-free radicals generated by xanthine oxidase during hypoxia-ischemia may result in cellular injury through harmful effects on membrane phospholipids. The present study investigated the effect of administration of allopurinol, an inhibitor of xanthine oxidase, on free-radical generation and brain cell membrane injury during hypoxia by inhibiting the breakdown of hypoxanthine to uric acid. Brain cell membrane Na+,K(+)-ATPase activity and lipid peroxidation products (conjugated dienes and fluorescent compounds) were determined as indices of brain membrane function and structure. Cerebral oxygenation was continuously monitored during hypoxia by 31P-NMR spectroscopy. Plasma and brain tissue levels of uric acid were measured to evaluate xanthine oxidase activity and purine degradation. Na+,K(+)-ATPase activity decreased significantly in both hypoxic groups; however, the allopurinol-treated hypoxic group showed a smaller decrease than the untreated hypoxic group (47.3 +/- 4.9 vs. 42.0 +/- 2.7 mumol Pi/mg protein/h, P < 0.05), respectively. Conjugated dienes increased significantly in the untreated hypoxic compared to control animals (0.070 +/- 0.045 vs. 0.004 +/- 0.006 mumol/g brain, P < 0.05), with the allopurinol-treated animals having intermediate values (0.053 +/- 0.039 mumol/g brain). Fluorescent compounds were lower in the allopurinol-treated hypoxic group compared to the untreated hypoxic group (0.79 +/- 0.19 vs. 1.06 +/- 0.60 micrograms/quinine sulfate/g brain, P < 0.05). Measurements of serum and brain tissue uric acid were significantly lower during hypoxia in the allopurinol-treated compared to the untreated group (30.3 +/- 15.6 vs. 45.7 +/- 10.6 microM (P < 0.05) and 1.69 +/- 0.97 vs. 4.27 +/- 2.37 nmol/g (P < 0.05), respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of allopurinol on uric acid levels and brain cell membrane Na+,K(+)-ATPase activity during hypoxia in newborn piglets. 795 82

Global ischemia, in the gerbil, produces profound hippocampal CA1 loss which leads to functional abnormalities (e.g. habituation impairment). In experiment 1, gerbils were subjected to 3 or 5 min of normothermic (brain) ischemia. Hypothermic groups were cooled to 32 degrees C for 12 h beginning 1 h after ischemia, while control groups (no hypothermia) regulated their own temperature. Exploration in a novel open field was assessed on days 3, 7 and 10 following ischemia and CA1 neurons were counted after 10- or 30-day survival. Both ischemia durations produced severe CA1 necrosis which resulted in increased open field activity. Hypothermia attenuated this behavioral pattern and substantially reduced CA1 necrosis against 3 min of ischemia when assessed at 10 and 30 days, but was only partially effective against a 5 min occlusion where, in addition, some cell death appeared to be delayed rather than prevented. In experiment 2, gerbils were occluded for 5 min and survived for 30 days. Twenty-four hours of hypothermia initiated 1 h after ischemia resulted in near total preservation of CA1 neurons. Thus, increasing the duration of post-ischemic hypothermia from 12 to 24 h produced much greater neuroprotection against severe ischemia. Prolonged post-ischemic hypothermia may be a valuable intervention in stroke patients.
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PMID:Delayed and prolonged post-ischemic hypothermia is neuroprotective in the gerbil. 798 76


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