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)

The effects of complete ischemia and of in vivo pharmacological treatment with trimetazidine were studied on some enzymatic activities related to energy transduction: lactate dehydrogenase for anaerobic glycolysis; citrate synthase and malate dehydrogenase for the Krebs' cycle; total NADH-cytochrome c reductase and cytochrome oxidase for the electron transport chain; glutamate dehydrogenase for amino acid metabolism and acetylcholine esterase for acetylcholine metabolism. These enzymatic activities were evaluated in brains of 10-day-old rats, at three different subcellular levels: homogenate in toto, purified mitochondrial fraction, crude, synaptosomal fraction. Complete normothermic post-decapitative ischemia of 30 min duration increased the activity of cytochrome oxidase in the homogenate in toto and increased the activities of citrate synthase and malate dehydrogenase in the purified mitochondrial fraction, the activities of the enzymes evaluated in the crude synaptosomal fraction being unaffected. The i.p. treatment with trimetazidine (at the dose level of 50 mg . kg-1) was without any significant effect on the tested enzymatic activities.
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PMID:Effects of ischemia and pharmacological treatment on subcellular fractions from neonatal rat brain. 628 22

There is a type of cerebral lesion, which kills neuronal cells at a later stage (greater than 48 hrs) post CA, while the systemic circulation is functioning normally. Although this lesion is probably dependent on multiple factors (----multiple therapies), a keyfactor in the pathogenesis is the loss of autoregulation and "finetuning" of the cerebral bloodflow according to local tissue metabolic needs. Although beneficial effect of almost none of the following therapies has been documented in randomised clinical studies, the following suggestions are made: a) In the CA-CPR phase: efficient respiratory care and external cardiac compressions (ECC), especially during bicarbonate administration; consider open chest CPR early, especially in cases of long arrest time and ineffective ECC. The socalled new CPR does not improve neurological outcome. b) In the post CPR phase: The non-autoregulated brain (cfr. focal ischemia) is kept preferentially at pCO2 values 25-30 mmHg, pO2 values greater than 100 mmHg, and normotension. Some form of stress, seizure and hyperthermia control prevents further imbalance metabolism/bloodflow. Relative dehydration, oncotic balance, steroids, early control of sepsis and uremia, early CT scan and measurement/control of ICP. All the above is currently grouped under "standard neuro-intensive therapy". Some other therapies, presently suggested by animal research are not very obvious, need first randomised clinical studies and are not suggested at this stage for clinical use: barbiturate coma, diphantoine, streptokinase, multifaceted therapy including hemodilution-brainflushing, Ca++ influx blocking drugs (lidoflazine). One such "innovative" therapy, barbiturate coma, has already been proven to be relatively ineffective (BRCT I) (Acta anaesth. belg., 1984, 25, suppl., 219-226).
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PMID:Brain protection in the immediate post-resuscitation phase. 651 33

The cerebrovascular resistance (CVR) of rat, and its dependence on stagnant blood or endothelial capillary swelling, was studied after 10 min of total ischemia by 10 s single carotid infusion of [14C]butanol in saline. The regional saline flow (CPR) was calculated from the uptake of [14 C]butanol. CVR was estimated at infusion pressures ranging from 8--25 kPa (60--190 mm Hg). At 14.7 kPa (110 mm Hg) infusion pressure, the regional CVR of the non-ischemic group varied between 0.21 and 0.40 kPa 100 g min ml-1. After 10 min of complete global cerebral ischemia, it increased to values between 0.82 and 1.95. Removal of blood from the brain by rinsing prior to ischemia did not change the CVR in ischemia. Increasing the plasma osmolality by 8% with mannitol before ischemia attenuated the CVR increase in ischemia. Thus, although osmotic swelling of endothelial cells contributed, the main cause of the CVR increase in ischemia was constriction of arterioles.
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PMID:Cerebrovascular resistance in ischemia. 678 47

The maximal rate of some cerebral enzymatic activities related to energy transduction (hexokinase; phosphofructokinase; lactate dehydrogenase; citrate synthase; malate dehydrogenase; total NADH-cytochrome c reductase; cytochrome oxidase), amino acid metabolism (glutamate decarboxylase; glutamate dehydrogenase) and cholinergic metabolism (acetylcholine esterase) were tested in the cerebral cortex and in sub-cortical area of rats. The evaluations were performed both in the homogenate in toto and in the crude mitochondrial fraction, before and after a postdecapitative normothermic ischemia of 5, 10, 20, and 40 min duration. The results are discussed also with respect to the pharmacological pretreatment with two biological substances which may modulate amino acid (L-alanine) and phospholipid metabolism (CDP-choline). The analysis of the present data suggests the occurrence in brain tissue of a variety of interrelated factors implicated in the ischemia-induced changes of the maximal rate of the enzymatic activities related to the energy transduction. These include: (a) rearrangement of the enzymatic activities because of the changed metabolic and chemico-physical condition; (b) decrease in the activity of enzymes related to the electron transfer chain and glycolysis; (c) changes in enzymes related to mitochondrial membranes. The effects of in vivo administration of alanine or CDP-choline, even if significant, are not consistent throughout the time period studied.
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PMID:Changes induced by ischemia on some cerebral enzymatic activities related to energy transduction and amino acid metabolism. 685 30

In this work we have employed a new extraction buffer for isolation of cardiac lysosomes from control and ischemia canine tissue. Compared to previous techniques, this buffer (0.6 M KCl, 0.25 M sucrose) enabled a 300% increase in the yield of particulate cardiac lysosomes and allowed acceptable levels of specific activity to be maintained. It also permitted great enrichment of a membrane-bound enzyme localized to a microsomal fraction, rotenone-insensitive NADH-cytochrome c reductase (RINCR). Ischemia was produced by ligation of the left anterior descending coronary artery for 2 hr, and myocardial blood flow (MBF) was measured using 85Sr labeled microspheres (15 microns). Enzymatic changes were measured in endocardial tissue of the ischemic left ventricular wall for comparison with control nonischemic samples. N-Acetyl-beta-glucosaminidase (NAG) was the most reliable lysosomal marker enzyme; this was depleted significantly (P < 0.001) in particulate lysosomal fractions; significant increases in the supernatant (P < 0.001) were found in areas of ischemia that were less than 25% of the control MBF. Lysosomal latency also diminished significantly during ischemia. Loss of total activity of RINCR in the microsomal fraction was highly significant (P < 0.001) in the areas of profound ischemia. The above data were compared with those from animals in which methylprednisolone (30 mg/kg) was administered 30 min prior to ligation of the coronary artery. Between the two groups (untreated versus methylprednisolone-treated animals) no significant differences could be found in total losses of NAG and RINCR or the rate at which these enzymatic changes ocurred. Lysosomal latency studies also revealed lack of significant changes between both groups. Thus, no significant "protective" effects of methylprednisolone could be found after 2 hr of ischemia.
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PMID:Lysosomal changes in an animal model of myocardial ischemia. Treatment with methylprednisolone. 742 51

Trimetazidine (TMZ) is an anti-ischemic compound whose precise mode of action is unknown, although several studies have suggested a metabolic effect, and there have been reports of protection of mitochondria against oxidative stress damage. Using a Langendorff rat heart model, we examined the effects of TMZ on the mitochondrial damage following 30 minutes of ischemia and 5 minutes of reperfusion. Mitochondrial respiration with succinate, glutamate-malate and ascorbate-N,N,N',N'-tetramethylphenylenediamine (TMPD) as substrates was significantly decreased following ischemia-reperfusion. Preperfusion with 10(-5) M TMZ had no effect on these rates in normoxic or ischemic hearts. However, 10(-3) M TMZ significantly decreased the glutamate-malate rate in mitochondria from normoxic hearts, and this rate was not further decreased following ischemia-reperfusion, and 10(-3) M TMZ also partially protected ascorbate-TMPD activity. The effect on glutamate-malate was probably due to an inhibition of complex I by TMZ, which specifically inhibited reduced nicotinamide-adenine-dinucleotide-cytochrome c reductase and complex I in lysed mitochondria. We also studied the effects of TMZ on the activity of pyruvate dehydrogenase (PDH) in normoxic and ischemic hearts perfused with 0.5 mM palmitate, which caused the enzyme to be almost completely inactivated. After short periods of ischemia (10-20 minutes) the PDH inactivation by palmitate was progressively lost. Preperfusion with 10(-5) M TMZ had a tendency to decrease lactate dehydrogenase release, accompanied by a maintenance of the inhibition of PDH by palmitate. This may allow the heart to oxidize fatty acids preferentially during reperfusion, hence removing possible toxic acyl esters.
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PMID:Trimetazidine effects on the damage to mitochondrial functions caused by ischemia and reperfusion. 764 24

Electron transport and production of O2-/H2O2 by the NADH dehydrogenase flavin-semiquinone (FMNH.) and ubisemiquinone (UQH.) were studied in a model of in vivo ischemia-reperfusion in rat kidney. H2O2 production rates were assessed in isolated mitochondria using either succinate, with and without antimycin, or malate-glutamate, with and without rotenone. Respiratory activities of isolated mitochondria and activity of NADH- and succinate-cytochrome c reductase and of NADH- and succinate-dehydrogenase in submitochondrial particles were measured to evaluate the electron flux throughout respiratory carriers. The mitochondrial H2O2 production rate was approximately 1.5- and 4-times increased in ischemic and ischemic-reperfused kidneys, respectively. Ischemia caused a marked decrease in the electron transport throughout the NADH-UQ segment with no significant changes either in the NADH dehydrogenase activity or in the electron flux trough the succinate-cytochrome oxidase segment. Reperfusion did not further affect the NADH-ubiquinone segment but markedly inhibited the succinate-supported oxygen consumption, succinate-cytochrome c reductase and succinate dehydrogenase activity. Our results show a redistribution of the electron flux with an increased rate of superoxide anion/hydrogen peroxide production at NADH dehydrogenase in mitochondria subjected to ischemia only. After 10 min reperfusion an impairment of the electron flow at succinate-cytochrome c segment is established and hydrogen peroxide production by UQH. increases up to maximal values becoming the major source of superoxide anion/hydrogen peroxide.
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PMID:Mitochondrial sites of hydrogen peroxide production in reperfused rat kidney cortex. 772 10

Non-synaptosomal and synaptosomal mitochondrial membrane-linked enzymatic activities, NADH-cytochrome c reductase rotenone insensitive (marker of the outer membrane) and cytochrome oxidase (marker of the inner membrane), were measured in rat brain hippocampus and striatum immediately after and 1, 4 and 7 days following the induction of complete transient ischemia (15 min) by the four vessel occlusion method. Furthermore citrate synthetase activity was measured with and without Triton X-100 in order to qualitatively evaluate the membrane permeability. Non-synaptosomal mitochondrial membranes showed reduction of both activities only in the late reperfusion phase: NADH-CCRRi decreased in striatal mitochondria after 4-7 days and only after 7 days in the hippocampus. COX activity decreased only in striatal mitochondria 7 days after ischemia. Non-synaptosomal mitochondrial membrane permeability did not show changes. Synaptosomal mitochondria showed a decrease of NADH-CCRRi only at 7 days of reperfusion both in hippocampus and striatum, while COX activity decreased only during ischemia and returned to normal levels in the following days in the two areas considered. In summary, free mitochondria showed insensitiveness to ischemia but they resulted damaged in the late reperfusion phase, while mitochondria from the synaptic terminal showed ischemic damage, partially restored during reperfusion. The striatal mitochondria showed a major susceptibility to ischemia/reperfusion damage, showing changes earlier than the hippocampal ones.
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PMID:Changes in non-synaptosomal and synaptosomal mitochondrial membrane-linked enzymatic activities after transient cerebral ischemia. 787 28

Since the 1985 Emergency Cardiac Care Conference, numerous controversies about the pharmacology of CPR have arisen (eg, questions about the pharmacokinetics and pharmacodynamics of drugs during CPR, the optimal vehicle for delivery of medications, and the dose of atropine in brady-asystolic cardiac arrest). This article has three objectives: 1) to critically explore these controversies, 2) to provide recommendations for clinical practice, and 3) to identify areas for future study. The ideal route is one which combines rapid access with quick delivery of drug to the central circulation. Because of hemodynamic changes during CPR, administration of drugs into the central circulation is preferable when compared with peripheral venous injection. Whenever drugs are administered from a peripheral i.v. site, the extremity should be elevated, and a 20-mL bolus of i.v. fluid should be given to facilitate access of the agent to the central circulation. If there is a delay in obtaining venous access, epinephrine, lidocaine, and atropine may be administered through the endotracheal tube at 2.5 times the i.v. dose. When administering these drugs through the endotracheal tube, dilute the drug in 10 mL of saline or water and inject it through a long catheter beyond the tip of the endotracheal tube. Dextrose 5% water is the primary vehicle for drug delivery during CPR. However, the administration of glucose during CPR is controversial because of the potentially detrimental effects of hyperglycemia on neuronal function during periods of ischemia. Data are inconclusive regarding the effects of glucose levels on neurologic outcome following resuscitation. Hyperglycemia may be a marker for prolonged resuscitation with subsequent impairment in insulin release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacologic controversies in CPR. 843 31

To improve emergency cardiac care (ECC) on the national or international level, we must translate to the rest of our communities the successes found in cities with high survival rates. In recent years, important developments have evolved in our understanding of the treatment and evaluation of cardiac arrest. Some of the most important of these developments include 1) recognition of the chain of survival, which is necessary to achieve high survival rates; 2) widespread acceptance that survival rates must be assessed routinely to ensure continuous quality improvements in the emergency medical services (EMS) system; and 3) development of improved methods for performing survival rate studies that will maximize the effectiveness of information gathering and analysis. While each community should determine how to optimize their own ECC services, some general guidelines are useful. Successful treatment of cardiac arrest starts in the community with prevention and education, including early recognition of the signs and symptoms of cardiovascular ischemia. Obtaining 911 service (and preferably enhanced 911) should be a top priority for all communities. EMS dispatchers should dispatch the unit to the scene in less than one minute, provide critical information to the responders regarding the type of emergency, and offer the caller telephone-assisted CPR instructions. The EMS first-responders should strive to arrive at the patient's side in less than four minutes, be able to immediately defibrillate if necessary, and begin basic CPR. An excellent strategy to accomplish this is to equip and train all fire-fighting units in the operation of automatic external defibrillators and dispatch them as a first-responder team. To manage the cardiac arrest patient, a minimum of two rescuers trained in advanced cardiac life support plus two or more rescuers trained in basic life support are needed. Furthermore, an EMS system is not complete without on-going evaluation. Therefore, the 1992 National Conference on CPR and ECC strongly endorses the position that all ECC systems assess their survival rates through an ongoing quality improvement process and that all members of the chain of providers should be represented in the outcome assessment team. We still have much to discover regarding optimal techniques of CPR, methods for data collection, and optimal structure of an EMS system. Research in these areas will provide the foundation for future changes in EMS systems development.
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PMID:Ensuring the effectiveness of community-wide emergency cardiac care. 843 34


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