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

Although hypokalemia has been reported after cardiac arrest and successful resuscitation, experimental data indicate that potassium is released from cells during ischemia. The purpose of this investigation was to study serum potassium concentration ([K+]) during closed chest cardiopulmonary resuscitation (CC-CPR) in humans. Twenty-two patients presenting to the emergency department (ED) in cardiopulmonary arrest had simultaneous measurement of central venous and arterial [K+] and blood gases during CC-CPR utilizing current advanced cardiac life support protocols and a pneumatic chest compressor and ventilator. Mean arterial and central venous [K+] were 5.0 +/- 1.3 and 5.6 +/- 2.9 mEq/L, respectively, (p greater than .05) with 7 patients having [K+] of greater than 6 mEq/L. Significant hyperkalemia does occur in some patients during cardiac arrest and CC-CPR. Because poor tissue perfusion during CC-CPR impairs exchange between the interstitial and intravascular compartments, increases in interstitial [K+] would be expected to be even greater. Interstitial hyperkalemia may play a role in the genesis of wide complex electromechanical dissociation (EMD) seen after prolonged cardiac arrest. Since calcium has long been known to be beneficial in the treatment of hyperkalemia-induced dysrhythmias, the success of calcium chloride in treating wide complex EMD may be on the basis of this phenomenon.
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PMID:Hyperkalemia during human cardiopulmonary resuscitation: incidence and ramifications. 278 2

Marker enzyme activities of different subcellular fractions were analyzed in cortex homogenates from rat kidney after different periods (15, 30, 60, and 90 min) of warm ischemia. Lactate dehydrogenase, alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, and succinate-cytochrome c reductase were not altered by ischemia in these periods. ATPase (2,4-dinitrophenol-stimulated and azide-sensitive), 5'-nucleotidase, K-Mg-nitrophenylphosphatase decline within 30 min of ischemia, whereas the microsomal enzymes glucose-6-phosphatase and NADPH-cytochrome c reductase decreased not before 60 min of ischemia. The early decrease of ATPase and of plasma membrane enzymes can be regarded as a consequence of membrane alterations. This enzymatic approach may be helpful to evaluate pharmacological agents for preventing and reserving ischemic effects in kidneys in a rational manner.
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PMID:Changed enzyme activities in rat kidney during ischemia. 286 6

Mitoplasts were prepared from 3-h ischemic livers in an attempt to define the structural alterations in the inner membrane that may account for the functional deficiencies of ischemic mitochondria. Mitoplasts from both control and ischemic livers had similar specific activities of cytochrome oxidase and succinate-cytochrome c reductase. With both preparations, the specific activity of rotenone-insensitive NADH-cytochrome c reductase was 10-fold lower than in the mitochondria from which they were prepared. Ischemic mitoplasts had no respiratory control with ADP, and had a slightly reduced phospholipid to protein ratio and an increased cholesterol to protein ratio. As a result, the cholesterol to phospholipid molar ratio was increased from the control of 0.04 to 0.08. There were also differences in the content of individual phospholipid species. Phosphatidylcholine increased by 15%, while cardiolipin decreased by 60%. There were increases in sphingomyelin and in the lysophospholipids of phosphatidylcholine, ethanolamine, and cardiolipin. Pretreatment with chlorpromazine did not prevent these changes. Linoleic acid was decreased by 35% in ischemic phospholipids, and the content of free fatty acids was increased 4-fold. Electron spin resonance spectroscopy of mitoplasts spin labeled with either 5- or 12-doxyl stearic acid revealed an increased molecular order (decreased fluidity) of ischemic inner mitochondrial membranes consistent with the increased cholesterol to phospholipid ratio. The data indicate activation of a phospholipase A in ischemic mitochondria with the resulting accumulation of products of lipid hydrolysis. This conclusion further emphasizes the close similarity between the structural and functional consequences of ischemia in the intact animal and the effect on isolated mitochondria of the activation of the endogenous phospholipase A. In both cases the major functional alterations are attributable to changes in the permeability of the inner mitochondrial membrane induced by the accumulation of lysophospholipids.
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PMID:Structural alterations of the inner mitochondrial membrane in ischemic liver cell injury. 298 20

The report deals with the effect of ischemia and reperfusion on purified sarcolemma obtained from canine myocardium of perfused supported heart preparations. Perfusion was carried out with a perfluorochemical (FC-43). Ischemia was produced by intermittent total clamping of inflow and outflow followed by release until the decrease in dP/dtmax had become stabile. Purity of sarcolemmal vesicles was ascertained with marker enzymes: succinate cytochrome c reductase (for mitochondria), K+-stimulated p-nitrophenylphosphate (K+-pNPPase), (Na+/K+)ATPase and adenylate cyclase (for SL). In addition Na+/Ca2+-exchange characteristics for SL were determined. Sidedness of vesicles was ascertained by means of adenylate cyclase activity using sarcolemmal preparations treated and untreated with alamethicin. Emphasis was placed on ATP-dependent Ca2+ uptake, phosphorylation of sarcolemmal vesicles and yield of SL proteins. Ischemia and reperfusion resulted in a significant reduction in adenylate cyclase activity. This decline was significant following ischemia and reperfusion. The yield of protein recovered from SL vesicles from ischemic-reperfused heart preparations was also significantly decreased. Both initial rate of ATP-dependent Ca2+ uptake and maximal Ca2+ uptake fell significantly following ischemia and reperfusion. The initial rate of phosphorylation also dropped significantly. These disturbances in SL Ca2+ transport following ischemia and reperfusion are probably a part of the general deficit in Ca2+ translocation.
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PMID:The effect of ischemia and reperfusion on sarcolemmal function in perfused canine hearts. 300 67

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

Although in vitro studies have demonstrated functional recovery of neurons after prolonged ischemia, in vivo experience with patients resuscitated from cardiopulmonary arrest demonstrates much less cerebral resistance to global ischemia. The purpose of our investigation was to compare the effectiveness of femoro-femoral veno-arterial cardiopulmonary bypass (CPB) to standard cardiopulmonary resuscitation in the treatment of prolonged cardiopulmonary arrest. Ten mongrel dogs were electrically fibrillated and left in cardiopulmonary arrest without any therapy for 12 minutes. Subsequently, either CPB (n = 5) or CPR (n = 5) was initiated and resuscitation attempted according to a standardized protocol that included administration of the calcium channel blocker lidoflazine in an effort to optimize cerebral and myocardial recovery. If there was return of spontaneous circulation, the animal was managed in an intensive care setting with invasive hemodynamic monitoring and ventilatory support for up to nine hours. Neurologic function was graded using a standardized neurologic deficit scoring (NDS) system at 12 hours after insult and daily for one week or until death. Prearrest hemodynamic and metabolic parameters were comparable in both groups (P greater than .05). All CPB animals were resuscitated successfully and alive at 24 hours after insult as opposed to none in the CPR group (P less than .005). In addition, three of the CPB animals were neurologically normal at final grading with NDS scores of zero. The other two CPB animals had persistent severe neurologic impairment and a mean NDS score of 51%. Thus CPB is more effective than CPR in the treatment of prolonged cardiopulmonary arrest. The improved outcome probably results primarily from improvement in blood flow with CPB.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiopulmonary bypass vs CPR as treatment for prolonged canine cardiopulmonary arrest. 357 65

Controlled clinically relevant animal models are essential in the ongoing search for increasingly cost-effective methods to reverse clinical death. Acute (up to 12 h) and short-term (up to 24 h) experiments are useful for the study of dying mechanisms and restoration of spontaneous circulation. Although long-term models are difficult and expensive, they are essential to permit lesions to mature, treatments to take effect, secondary deterioration to be recognized, and survival and brain damage to be quantified and compared between treatment groups. The insults studied include temporary complete global head ischemia in monkeys, ventricular fibrillation cardiac arrest in dogs, asphyxial cardiac arrest in rats and dogs, and exsanguination arrest in dogs. Standard external CPR combined with advanced life support is less successful than open-chest CPR or emergency cardiopulmonary bypass after prolonged ventricular fibrillation. Postinsult monitoring of multiple organ systems can be used to explore the postresuscitation syndrome and evaluate novel treatment potentials. Outcome measurements include brain enzyme leakage into the cerebrospinal fluid, neurologic deficit scoring, overall performance categorization, incidence of secondary deterioration, and histopathologic damage scoring of brain and viscera.
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PMID:Long-term animal outcome models for cardiopulmonary-cerebral resuscitation research. 393 81

Although recent clinical reports have noted hypokalemia after resuscitation from cardiac arrest, extensive animal work indicates that potassium is released from cells during ischemia. This study was undertaken to define the changes that occur in serum potassium ion during cardiac arrest and resuscitation in a canine model. Fourteen dogs were subjected to 5 min of cardiac arrest followed by 30 min of closed-chest CPR (CCPR). Resuscitation was performed according to a standardized protocol. Serum potassium increased significantly (p less than .001) from baseline, remained elevated 5 min after return of spontaneous circulation (ROSC), but declined to baseline levels at 15 min post-ROSC. Increases in interstitial potassium would be expected to be even greater due to the poor exchange between interstitial and intravascular compartments during CCPR. Interstitial hyperkalemia may play a role in the genesis of wide-complex electromechanical dissociation and may explain the reported success of calcium chloride in treating this problem.
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PMID:Hyperkalemia during cardiac arrest and resuscitation in the canine model. 395 20

Changes in the maximal rate of some cerebral enzymatic activities related to 400ene transduction and neurotransmission (lactate dehydrogenase; citrate synthase and malate dehydrogenase; total NADH-cytochrome c reductase and cytochrome oxidase; glutamate dehydrogenase; acetylcholine esterase) were assayed both in the crude or purified mitochondrial fraction and in the crude synaptosomal fraction from rat whole brain or cerebral cortex. The evaluations were performed in rats before and after a postdecapitative normothermic ischemia of 5, 10, 20 and 40 min duration. Modification observed in some of these activities wer discussed for comparison with other experimental results from different researchers. At present no definite conclusions can be drawn, but certainly the observed modifications in activity of enzymes are not passive but expression of deranged metabolism of ischemic neurons.
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PMID:Brain enzymes and ischemia. 626 30


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