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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although no specific pharmacologic therapy for clinical application to cerebral resuscitation after ischemia exists, biochemically guided mechanistic studies are under way to unravel what appears to be an extremely complex process. The evolution of the primary parenchymal insult after ischemia in the brain appears to be coupled to a multifactorial interaction between blood and damaged brain tissue that is initiated very rapidly during reperfusion and leads to further tissue injury (Fig. 8). Current studies implicate calcium, oxyradicals, phospholipid-derived metabolites, and blood elements as possible mediators of tissue injury during reperfusion. However, the optimal conditions for repair and ongoing metabolism after ischemia remain to be defined. In this regard, studies to investigate postischemic communication failure, optimal active and basal metabolic rate in the postischemic brain, and optimal pressure and flow patterns during reperfusion are needed to guide future therapies. Future therapies based on these alternative approaches could supplement refined versions of the regimens presented in this article--those that attempt to minimize reperfusion injury. Meaningful progress in the mitigation of postischemic encephalopathy is almost certain to require novel, specific therapies used in multimodal regimens with a significant fraction of the agents administered as near as possible to the onset of reperfusion. To develop these regimens to treat the pediatric arrest, studies in pediatric models or at least models of asphyxial arrest are essential.
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PMID:Novel pharmacologic approaches to brain resuscitation after cardiorespiratory arrest in the pediatric patient. 314 Oct 11

Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.
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PMID:Etiologic and preventive aspects of epilepsy in the child--bridging the gap between laboratory and clinic. 330 92

Seventy-two patients who underwent orthotopic liver transplantation (OLT) were studied to identify perioperative variables that would predict survival and intraoperative blood loss. Survival and intraoperative blood loss were not affected by encephalopathy, length of donor liver ischemia, or any of the preoperative laboratory values studied. Survival was significantly decreased in patients requiring postoperative dialysis (41%) and in patients who had severe rejection requiring retransplantation (33%). Intraoperative blood loss was significantly greater in patients over 50 years of age (11.6 blood volumes) and patients with biliary atresia (8.7 blood volumes). These results may aid in choosing future recipients for orthotopic liver transplantation and in anticipating the postoperative support needed.
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PMID:Variables influencing the outcome following orthotopic liver transplantation. 331 Sep 60

In seven entirely healthy children in the age group of 6.5 to 14.5 years, mild head injury produced transient global amnesia (TGA) of median duration of 4.5 hours. None of the patients had convincing signs of brain concussion or clinical focal symptomatology. In four cases CT examination of the brain showed normal findings. Four children had a transient abnormal EEG (intermittent delta rhythms, slowed background activity inconstant local finding (of slow waves). During the period monitored (2-34 months) there was no recurrent attack and the children have had no difficulties. Pathologically, the authors assume ischemia of temporobasal structures induced by mild trauma with a relationship to migraine diathesis and rank the child group among so called benign posttraumatic encephalopathy with a noncomplicated course and good outcome.
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PMID:Transient global amnesia after mild head injury in childhood. 338 47

Since its introduction in 1960, CPR has evolved into a complex program involving not only the medical community but also the lay public. Currently, program activities include instruction of the lay public in basic life support techniques, development and deployment of emergency medical systems, recommendations for drug protocols for advanced cardiac life support and, most recently, introduction of new methods for tissue protection following resuscitation. After 25 years of experience, we are beginning to understand the pathophysiology of tissue ischemia during cardiac arrest and the interventions required to improve chances of survival and quality of life of the cardiac arrest victim. Recent data in the literature suggest that modification of certain interventions in the resuscitation program may be needed. The poor neurologic outcomes with prolonged standard CPR show that it is not protective after 4 to 6 minutes of cardiac arrest. Modifications to this technique, including SVC-CPR or IAC-CPR, have not been shown to increase resuscitability or hospital discharge rates. Human studies of open-chest cardiac massage are needed to evaluate this option. Defibrillation is the definitive treatment for ventricular fibrillation. Greater emphasis should be placed on the earliest possible delivery of this treatment modality. Computerized defibrillators may provide greater and earlier access to defibrillation in the homes of patients at high risk of ventricular fibrillation. They may also be applicable by untrained public service personnel (police and firemen), individuals in geographically inaccessible areas (aircraft), or emergency medical technicians in rural areas where skill retention is a significant problem. Calcium has no proved benefit in cardiac resuscitation. There is biochemical evidence that it may be harmful in brain resuscitation. Its use in resuscitation should be discontinued. The dose of epinephrine currently advocated in the ACLS protocols may be inadequate to increase aortic diastolic pressure and coronary and cerebral perfusion pressures and thus aid resuscitation. Animal studies indicate that substantial increases in the current dosage are needed to achieve these effects. Human studies are needed to verify these results. A role for calcium antagonists in the treatment of postarrest encephalopathy has been demonstrated in animals and is currently undergoing clinical trials. Iron-dependent lipid peroxidative cell membrane injury may be important in the pathogenesis of postarrest encephalopathy. Animal studies suggest that the iron chelator deferoxamine may have a significant therapeutic role in the treatment of postarrest encephalopathy.
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PMID:Ischemia, resuscitation, and reperfusion: mechanisms of tissue injury and prospects for protection. 351 7

Cerebral neurons can tolerate at least 20 min of normothermic ischemic anoxia. Cerebral recovery from more than 5 min of cardiac arrest is hampered by complex secondary derangements of multiple organ systems after reperfusion. There is increasing support of our hypothesis that this "postresuscitation syndrome" includes the following: secondary cerebral perfusion failure, cerebral reoxygenation injury (cell-necrotizing cascades), and cerebral "intoxication" from derangements of extracerebral organs. To be optimal for the brain, CPR with optimal perfusion pressure must be started as promptly as possible. Significant though inconsistent mitigation of permanent brain damage after prolonged complete global brain ischemia has been achieved in animal outcome preparations with the use of the following treatments initiated at the start of reperfusion: brain-oriented extracerebral life support by protocol, intra-arterial hemodilution, hypertension, and artificial circulation, barbiturates, calcium-entry blockers, free-radical scavengers, and multifaceted treatments. We currently recommend treatment 1 for patient care and treatment 2 for clinical feasibility trials. Treatment 3, thiopental loading (starting 10 to 50 min after restoration of spontaneous circulation), was tested in a randomized clinical trial and was not shown to confer a statistically significant benefit. A calcium-entry blocker is under clinical investigation. Many other novel treatments appear promising but further animal studies are required. The complex multifactorial pathogenesis of postcardiac arrest encephalopathy requires systematic multicenter development of etiology-specific combination therapies.
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PMID:Cerebral resuscitation after cardiac arrest: a review. 353 60

The pathological changes in the brains of seven patients who had been clinically diagnosed as normal pressure hydrocephalus (NPH) are described and the possible etiological mechanisms are discussed. The pathological findings in all cases consisted of demyelination akin to Binswanger's type of encephalopathy, especially in the frontal lobes. Arteriosclerosis accompanied by occasional organized thrombi and scattered microinfarcts in the periventricular white matter were seen. Focal leptomeningeal fibrosis, diminution of arachnoidal granulations, and non-specific aging processes were noted. Among the above of particular interest, was the degeneration of both periventricular and deep white matters with microinfarcts, and moderate to severe arteriosclerosis. On the basis of these observations, we assume that the degeneration in the white matter is not merely a secondary change due to the result of enlargement of ventricle, but plays an important role in the development of NPH. The development of NPH requires not only the disturbance of cerebrospinal fluid, but also the pre- or coexisting vulnerability in the white matter caused by variables such as ischemia, hypoxia, and trauma.
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PMID:Normal pressure hydrocephalus. Neuropathological study. 357 65

We examined the impact of pre-treatment with the calcium antagonist flunarizine on the development of hypoxic-ischemic brain injury in the immature rat. Unilateral carotid artery ligation and subsequent exposure to 2 hours of 8% oxygen in 7-day-old rats was used as a model for perinatal hypoxic-ischemic encephalopathy. This procedure leads to atrophy in the cerebral hemisphere ipsilateral to carotid occlusion, with prominent foci of neuronal infarction in the caudate-putamen (striatum). The morphologic injury develops after 1 1/2 hours of hypoxia; and there is an equivalent time threshold for duration of hypoxic exposure needed to acutely stimulate dopamine release in the ipsilateral striatum. Parenteral administration of 30 mg/kg of flunarizine before hypoxic exposure limited both the release of dopamine acutely and the extent of morphologic damage observed two weeks after the insult. Oral administration of 30 mg/kg of flunarizine in a different vehicle prevented morphologic damage but had no effect on stimulated dopamine release. The drug vehicle for the parenteral preparation also prevented tissue injury, but to a lesser degree than flunarizine. However the parenteral vehicle was equipotent with parenteral flunarizine in limiting acute stimulation of dopamine release. The results demonstrate that flunarizine has potent neuroprotective properties against morphologic brain injury from hypoxia-ischemia, acting by a mechanism which is independent of effects on dopamine release.
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PMID:Flunarizine limits hypoxia-ischemia induced morphologic injury in immature rat brain. 371 46

A model of transient acute hepatic failure has been developed in the pig. Three days after a functional end-to-side portacaval shunt was introduced, 15 ambulant animals underwent total liver ischemia for 4 to 6 h by the closure of a mechanical clamp surrounding the hepatic artery. Four of the eight animals subjected to 4 hr of ischemia survived. All but one of the animals undergoing 6 hr of hepatic ischemia developed grade 4 encephalopathy after 24 to 30 hr and died within 50 hr. Quantitative estimation of liver cell necrosis revealed less than 40% necrosis in the survivors, and approximately 62% (range 49-75%) in animals who died of hepatic coma. As far as the putative toxins are concerned, significant differences were found between animals undergoing 4 and those undergoing 6 hr of ischemia, especially in the plasma ammonia levels and the plasma ratios for tyrosine and phenylalanine. Plasma arginine levels had fallen to zero in both groups at 24 hr and only rose to preischemic values in animals who survived. This large animal model fulfills the accepted criteria of potential reversibility, reproducibility, and death due to hepatic failure.
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PMID:A reproducible model of acute hepatic failure by transient ischemia in the pig. 380 58

We compared the levels of hormones and metabolites in the plasma of 37 survivors of Reye's syndrome with the levels in 8 fatal cases, at four time periods within 72 hours of admission. The most prominent differences were found for norepinephrine (NE), which was significantly elevated in fatal cases compared with survivors at all periods. Lactate and dopamine were elevated in the earlier periods. Epinephrine and alpha-amino acid nitrogen were also elevated in fatal cases, but the differences usually were not significant. NE elevation may reflect an increased sympathoadrenal medullary output associated with brain edema, compounded by impaired hepatic clearance of monoamines. Skeletal muscle ischemia from NE-induced vasoconstriction may explain the association between lactic acidemia and the severity of encephalopathy.
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PMID:The metabolic course of Reye's syndrome: distinction between survivors and nonsurvivors. 395 18


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