UMLS:C0022116 - FACTA Search

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

We have investigated the effects of isoflurane and desflurane on neurological outcome in a rat model of incomplete cerebral ischaemia. We studied 40 non-fasted male Sprague-Dawley rats, anaesthetized, intubated and ventilated mechanically with isoflurane and nitrous oxide in oxygen (FlO2 0.3). Arterial and venous catheters were inserted for measurement of arterial pressure, drug administration and blood sampling. A biparietal electroencephalogram (EEG) was recorded continuously using subdermal platinum electrodes. At completion of surgery, administration of isoflurane was discontinued (with the exception of those animals receiving isoflurane as treatment) and rats were allowed an equilibration period of 30 min according to the following procedure: group 1 (n = 10), 66% nitrous oxide in oxygen and fentanyl (bolus 10 micrograms kg-1 i.v. followed by infusion at a rate of 25 micrograms kg-1 h-1); group 2 (n = 10), 1.0 MAC of isoflurane in oxygen (FlO2 0.3) and air; groups 3 and 4 (n = 10 per group), 1.0 MAC or 1.5 MAC of desflurane in oxygen (FlO2 0.3) and air, respectively. Ischaemia was produced by combined unilateral common carotid artery ligation and haemorrhagic hypotension to 35 mm Hg for 30 min. Functional neurological deficit was evaluated for 3 days after cerebral ischaemia. At baseline, brain electrical activity was higher with fentanyl-nitrous oxide, 1.0 MAC of isoflurane and 1.0 MAC of desflurane (groups 1-3) compared with 1.5 MAC of desflurane (group 4). Neurological outcome was improved in isoflurane and desflurane anaesthetized animals (groups 2-4), regardless of the concentration used compared with fentanyl-nitrous oxide anaesthesia (group 1). The increase in plasma epinephrine and norepinephrine concentrations during ischaemia was significantly higher in fentanyl-nitrous oxide anaesthetized animals (group 1) compared with animals who received volatile anaesthetics (groups 2-4). These data suggest that cerebral protection produced by isoflurane and desflurane appears to be related to reduction in sympathetic activity rather than suppression of cerebral metabolic rate.
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PMID:Desflurane and isoflurane improve neurological outcome after incomplete cerebral ischaemia in rats. 1065 12

Protein kinase C (PKC) is an important enzyme involved in the regulation of neurotransmission and might also be important in the mediation of ischemic neuronal death. PKC has been implicated as a target of volatile anesthetics as well as in anesthetic protection against ischemia. The present study tested the effect of isoflurane and sevoflurane, both used in neuroanesthetic practice, on presynaptic free cytosolic Ca2+ ([Ca2+](i)) and PKC activity. To measure [Ca2+](i) and PKC activation simultaneously, rat synaptosomes, mostly containing presynaptic terminals, were loaded with the fluorescent probes fura-2 and fim-1, respectively. The synaptosomes were exposed to either isoflurane or sevoflurane in concentrations corresponding to 1 and 2 MAC values in rats, both in Ca2+-containing and Ca2+-free medium. After 8 minutes of anesthetic exposure, 1 mM 4-aminopyridine was added to induce membrane depolarization. Isoflurane 1 and 2 MAC increased the basal PKC activity after 8 minutes in Ca2+-containing medium by 15.1% (3.6%) and 30.5% (5.5%) compared with control, respectively [mean (SEM); n = 9, both values P < 0.05]. Sevoflurane 2 MAC transiently decreased but thereafter increased the PKC activity (P < 0.05). In Ca2+ -free medium sevoflurane attenuated the PKC activity (P < 0.05). The anesthetics did not alter the depolarization-evoked enzyme activation. Furthermore, 2 MAC of both isoflurane and sevoflurane increased the basal- and attenuated the depolarization-evoked increase in [Ca2+](i) (P < 0.05). The present study supports the hypotheses that volatile anesthetics affect presynaptic PKC activity and that the anesthetic effect on enzyme activation seems to be related to an increase in [Ca2+](i).
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PMID:The effect of isoflurane and sevoflurane on cerebrocortical presynaptic Ca2+ and protein kinase C activity. 1282 68

Nitric oxide (NO) is the mediator of ischemic preconditioning against myocardial infarction. Desflurane produces anesthetic preconditioning to protect the myocardium against infarction. In the model of myocardial ischemia-reperfusion injury in rabbits, we evaluated desflurane-induced ischemic preconditioning and studied its mechanism of NO synthesis. Thirty-two male adult New Zealand white rabbits were anesthetized with intravenous (IV) 30 mg/kg pentobarbital followed by 5 mg/kg/hr infusion. All rabbits were subjected to 30 minutes (min) long lasting left anterior descending coronary artery (LAD) occlusion and three hours (hr) of subsequent reperfusion. Before LAD occlusion, the rabbits were randomly allocated into four groups for preconditioning treatment (eight for each group). The control group did not receive any preconditioning treatment. The desflurane group received inhaled desflurane 1.0 MAC (minimal end-tidal alveolar concentration) for 30 min that was followed by a 15 min washout period. The L-NAME-desflurane group received L-NAME (NG-nitro-L-arginine methyl ester; non-selective Nitric Oxide Synthetase (NOS) inhibitor) 1 mg/kg IV 15 min before 1.0 MAC inhaled desflurane for 30 min. The L-NAME group received L-NAME 1 mg/kg IV. Infarct volume, ventricular arrhythmia, plasma lactate dehydrogenase (LDH), creatine kinase (CK) activity and myocardial perfusion were recorded simultaneously. We have found that hemodynamic values of the coronary blood flow before, during, and after LAD occlusion were not significantly different among these four groups. For the myocardial ischemia-reperfusion injury animals, the infarction size (mean +/- SEM) in the desflurane group was significantly reduced to 18 +/- 3% in the area at risk as compared with 42 +/- 7% in the control group, 35 +/- 6 in the L-NAME group, and 34 +/- 4% in the L-NAME-desflurane group. The plasma LDH, CK levels, and duration of ventricular arrhythmia were also significantly decreased in the desflurane group during ischemia-reperfusion injury. Our results indicate that desflurane is an anesthetic preconditioning agent, which could protect the myocardium against the ischemia-reperfusion injury. This beneficial effect of desflurane on the ischemic preconditioning is probably through NO release since L-NAME abrogates the desflurane preconditioning effect.
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PMID:Effect of desflurane-induced preconditioning following ischemia-reperfusion on nitric oxide release in rabbits. 1556 90

It has been suggested that N2O may alter the sensitivity of the brain to ischemia. To test this hypothesis. we examined the effects of N2O on the development of left-right hemispheric asymmetry in the electroencephalogram (EEG) during hemorrhagic hypotension in rats subjected to unilateral carotid occlusion. Rats were anesthetized with halothane/O2/air, and ventilated to normocarbia (PaCO2 approximately 40 mm Hg). Catheters were placed in the femoral artery and vein, and both common carotid arteries (CCA) were exposed. Bilateral fronto-occipital screws were then placed to record left and right hemispheric EEGs, which were processed by computer and stored on disc. Animals were then randomly assigned to one of three treatment groups (n = 8 each): group 1, 0.5 MAC (0.5%) halothane + 0.5 MAC (70%) N2O; group 2, 1 MAC (1.0%) halothane + 70% nitrogen; and group 3, 1 MAC halothane + 70% N2O. After stabilization, the left CCA were occluded. Animals with EEG changes at this point were discarded. Beginning 5 min later, venous blood withdrawal was started at a rate of 0.25 ml/min, while mean arterial blood pressure (MAP) and EEG were continuously recorded. After exsanguination was complete, EEG data (raw and processed) were re-examined by an individual who was unaware of the anesthetics administered to determine the MAP at which any evidence of EEG asymmetry appeared. There were no intergroup differences in weight, PaO2, PaCO2, pHa, blood glucose. hematocrit, or starting (prebleed) MAP. The earliest change in the EEG was typically a decrease in total amplitude over the hemisphere ipsilateral to the carotid occlusion. Adding 70% N2O to a 1 MAC halothane background (group 2 vs. group 3) had no effect on the MAP at which this EEG asymmetry appeared (54 +/- 13 vs. 53 +/- 10 mm Hg). However, this MAP was significantly higher in animals breathing 0.5 MAC halothane + 0.5 MAC N2O (group 1, 78 +/- 17 mm Hg, p = 0.0019 by ANOVA). We conclude that 70% N2O had no direct effects on the MAP at which EEG abnormalities appear (group 2 vs. 3), and that the observed differences are more closely related to the concentration of volatile agent. Whether these differences are related to anesthetic-induced differences in the brain's tolerance to reduced CBF or whether there are differences in cerebral blood flow (CBF) autoregulation are unknown.
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PMID:EEG changes during carotid occlusion and hypotension in the rat: the effects of nitrous oxide. 1581 50

Volatile anesthetics induce myocardial preconditioning and can also protect the heart when given at the onset of reperfusion-a practice recently termed "postconditioning." We investigated the role of mitochondrial KATP (mKATP)-channels in sevoflurane-induced cardioprotection for both preconditioning and postconditioning alone and whether there is a synergistic effect of both. Rats were subjected to 25 min of coronary artery occlusion followed by 120 min of reperfusion. Infarct size was determined by triphenyltetrazolium staining. The following protocols were used: 1) preconditioning (S-Pre, n = 10, achieved by 2 periods of 5 min sevoflurane administration (1 MAC) followed by 10 min of washout); 2) sevoflurane postconditioning (1 MAC of sevoflurane given for 2 min at the beginning of reperfusion; S-Post, n = 10); 3) administration before and after ischemia (S-Pre + S-Post, n = 10). Protocols 1-3 were repeated in the presence of 5-hydroxydecanoate (5HD), a specific mKATP-channel-blocker (S-Pre + S-Post + 5HD, S-Pre + 5HD: n = 10; S-Post + 5HD: n = 9). Nine rats served as untreated controls (CON) or received 5HD alone (5HD, n = 10). Both S-Pre (23% +/- 13% of the area at risk, mean +/- sd) and S-Post (18% +/- 5%) reduced infarct size compared with CON (49% +/- 11%, both P < 0.05). S-Pre + S-Post resulted in a larger reduction of infarct size (12% +/- 5%, P = 0.054 versus S-Pre) compared with administration before or after ischemia alone. 5HD diminished the protection in all three sevoflurane treated groups (S-Pre + 5HD, 35% +/- 12%; S-Post + 5HD, 44% +/- 12%; S-Pre + S-Post + 5HD, 46% +/- 14%;) but given alone had no effect on infarct size (41% +/- 13%). Sevoflurane preconditioning and postconditioning protects against myocardial ischemia-reperfusion injury. The combination of preconditioning and postconditioning provides additive cardioprotection and is mediated, at least in part, by mKATP-channels.
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PMID:The influence of mitochondrial KATP-channels in the cardioprotection of preconditioning and postconditioning by sevoflurane in the rat in vivo. 1624 77

Inhibition of glycogen synthase kinase (GSK)-beta protects against ischemia-reperfusion injury. Brief exposure to isoflurane before and during early reperfusion after coronary artery occlusion also protects against infarction. Whether GSK-beta mediates this action is unknown. We tested the hypothesis that GSK inhibition enhances isoflurane-induced postconditioning. Rabbits (n = 88; 6 to 7 per group) subjected to a 30-min coronary occlusion followed by 3 h reperfusion received saline, isoflurane (0.5 or 1.0 minimum alveolar concentration [MAC]) administered for 3 min before and 2 min after reperfusion, the selective GSK inhibitor SB216763 (SB21; 0.2 or 0.6 mg/kg), or 0.5 MAC isoflurane plus 0.2 mg/kg SB21. Other groups of rabbits pretreated with phosphatidylinositol-3 kinase (PI3K) inhibitor wortmannin (0.6 mg/kg), 70-kDa ribosomal protein s6 kinase (p70s6K) inhibitor rapamycin (0.25 mg/kg), or mitochondrial permeability transition pore (mPTP) opener atractyloside (5 mg/kg) received 0.6 mg/kg SB21 or 0.5 MAC isoflurane plus 0.2 mg/kg SB21. Additional groups received the mPTP inhibitor, cyclosporin A (5 mg/kg), plus 0.2 mg/kg SB21 with or without atractyloside pretreatment. Isoflurane (1.0 but not 0.5 MAC) and SB21 (0.6 but not 0.2 mg/kg) reduced (P < 0.05) infarct size (21% +/- 5%, 44% +/- 7%, 23% +/- 4%, and 46% +/- 2%, respectively, of left ventricular area at risk, mean+/- sd; triphenyltetrazolium staining) as compared with control (42% +/- 6%). Isoflurane (0.5 MAC) plus 0.2 mg/kg SB21 and cyclosporin A plus 0.2 mg/kg SB21 produced similar degrees of protection (24% +/- 4% and 27% +/- 6%, respectively). Atractyloside but not wortmannin or rapamycin abolished protection produced by 0.6 mg/kg SB21 and 0.5 MAC isoflurane plus 0.2 mg/kg SB21. Thus, GSK inhibition enhances isoflurane-induced protection against infarction during early reperfusion via a mPTP-dependent mechanism.
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PMID:Inhibition of glycogen synthase kinase enhances isoflurane-induced protection against myocardial infarction during early reperfusion in vivo. 1663 7

Brief exposure to isoflurane or repetitive, transient ischemia during early reperfusion after prolonged coronary artery occlusion protects against myocardial infarction by inhibiting the mitochondrial permeability transition pore (mPTP). Inhibition of mPTP during delayed ischemic preconditioning occurred concomitant with enhanced expression of the antiapoptotic protein B cell lymphoma-2 (Bcl-2). We tested the hypothesis that Bcl-2 mediates myocardial protection by isoflurane or brief ischemic episodes during reperfusion in rabbits (n = 91) subjected to a 30-min left anterior descending coronary artery occlusion followed by 3 h reperfusion. Rabbits received 0.9% saline, isoflurane (0.5 or 1.0 minimum alveolar concentration, MAC) administered for 3 min before and 2 min after reperfusion, 3 cycles of postconditioning ischemia (10 or 20 s each) during early reperfusion, 0.5 MAC isoflurane plus 3 cycles of postconditioning ischemia (10 s), or the direct mPTP inhibitor cyclosporin A (CsA, 10 mg/kg) in the presence or absence of the selective Bcl-2 inhibitor HA14-1 (2 mg/kg, i.p.). Isoflurane (1.0, but not 0.5, MAC) and postconditioning ischemia (20 s but not 10 s) significantly (P < 0.05) reduced infarct size (mean +/- sd, 21% +/- 4%, 43% +/- 7%, 19% +/- 7%, and 39% +/- 11%, respectively, of left ventricular area at risk) as compared with control (44% +/- 4%). Isoflurane (0.5 MAC) plus 10 s postconditioning ischemia and CsA alone also exerted protection. HA14-1 alone did not affect infarct size nor block protection produced by CsA but abolished reductions in infarct size caused by 1.0 MAC isoflurane, 20 s postconditioning ischemia, and 0.5 MAC isoflurane plus 10 s postconditioning ischemia. The results suggest that Bcl-2 mediates isoflurane-induced and ischemic postconditioning by indirectly modulating mPTP activity in vivo.
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PMID:The influence of B-cell lymphoma 2 protein, an antiapoptotic regulator of mitochondrial permeability transition, on isoflurane-induced and ischemic postconditioning in rabbits. 1663 8

Volatile anesthetics isoflurane possibly improves the ischemic brain injury. However, its molecular actions are still unclear. In ischemia, protein kinase C (PKC)gamma and calcium/calmodulin dependent protein kinase II (CaMKII)-alpha are persistently translocated from cytosol to cell membranes, and diminish these translocation suggested to be neuroprotective. We thus tested a hypothesis that isoflurane inhibits PKCgamma and CaMKII-alpha translocation after ischemic brain insults. C57Bl/6J male mice were made to inhale 1 or 2 MAC isoflurane, after which 3 or 5 min cerebral ischemia was induced by decapitation. The sampled cerebrum cortex was then homogenized and centrifuged into crude synaptosomal fractions (P2), cytosolic fractions (S3), and particulate fractions (P3). CaMKII-alpha and PKCgamma levels of these fractions were analyzed by immunoblotting. PKCgamma and CaMKII-alpha are translocated to synaptic membrane from cytosol by cerebral ischemia, although isoflurane significantly inhibited such translocation. These results may explain in part the cellular and molecular mechanisms of neuroprotective effects of isoflurane.
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PMID:Isoflurane inhibits protein kinase Cgamma and calcium/calmodulin dependent protein kinase ii-alpha translocation to synaptic membranes in ischemic mice brains. 1847 71

Activation of the complement cascade represents an important event during ischemia/reperfusion injury (IRI). This work was designed to investigate the role of the membrane attack complex (MAC; C5b-9) in the pathogenesis of hepatic IRI. Livers from B&W/Stahl/rC6(+) and C6(-) rats were harvested, stored for 24 hours at 4 degrees C, and then transplanted [orthotopic liver transplantation (OLT)] to syngeneic recipients. There were 4 experimental groups: (1) C6(+)-->C6(+), (2) C6(+)-->C6(-), (3) C6(-)-->C6(+), and (4) C6(-)-->C6(-). At day +1, C6(-) OLTs showed decreased vascular congestion/necrosis, contrasting with extensive necrosis in C6(+) livers, that was independent of the recipient C6 status (Suzuki score: 7.2 +/- 0.9, 7.3 +/- 1.3, 4.5 +/- 0.6, and 4.8 +/- 0.4 for groups 1-4, respectively, P < 0.05). The liver function improved in recipients of C6(-) grafts (serum glutamic oxaloacetic transaminase: 2573 +/- 488, 1808 +/- 302, 1170 +/- 111, and 1188 +/- 184 in groups 1-4, respectively, P < 0.05). Intragraft macrophage infiltration (ED-1 immunostaining) and neutrophil infiltration (myeloperoxidase activity) were reduced in C6(-) grafts versus C6(+) grafts (P = 0.001); these data were confirmed by esterase staining (naphthol). The expression of proinflammatory interferon-gamma, interleukin-1beta, and tumor necrosis factor messenger RNA/protein was also reduced in C6(-) OLTs in comparison with C6(+) OLTs. Western blot-assisted expression of proapoptotic caspase-3 was decreased in C6(-) OLTs versus C6(+) OLTs (P = 0.006), whereas antiapoptotic Bcl-2/Bag-1 was enhanced in C6(-) OLTs compared with C6(+) OLTs (P = 0.001). Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling staining of apoptotic cells was enhanced (P < 0.05) in C6(+) OLTs compared with C6(-) OLTs. Thus, the terminal products of the complement system are essential in the mechanism of hepatic IRI. This is the first report using a clinically relevant liver cold ischemia model to show that local MAC inhibition attenuates IRI cascade in OLT recipients.
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PMID:The membrane attack complex (C5b-9) in liver cold ischemia and reperfusion injury. 1866 46

Apoptotic cells are potent complement activators; and proposed mechanisms include IgM-mediated classical pathway activation, C-reactive protein (CRP)-mediated classical pathway activation, and IgM-mediated lectin pathway activation. While complement activation is beneficial in clearing apoptotic cells, the resulting complement-mediated inflammation may extend damage to the surrounding cells and tissues, as observed in ischemia/reperfusion injury. We previously engineered and characterized a single-chain Fv against C1q globular heads (scFv(QuVHVL)) that blocked C1q binding to immobilized IgG and to IgG-sensitized cells, and thereby inhibited IgG-mediated classical pathway activation [Hwang H.Y., Duvall M.R., Tomlinson S., Boackle R.J., 2008. Highly specific inhibition of C1q globular-head binding to human IgG: a novel approach to control and regulate the classical complement pathway using an engineered single-chain antibody variable fragment. Molecular Immunology 45, 2570-2580]. In the present study, this scFv(QuVHVL) was examined for its ability to restrict complement deposition on apoptotic cells in the presence of fresh normal human serum (NHS). Interestingly, the addition of scFv(QuVHVL) to NHS decreased C1-mediated C4b deposition on apoptotic cells by 60% as compared to appropriate buffer-treated control serum. By inhibiting initiation of the early complement components, the subsequent C3b and membrane attack complex depositions were inhibited by 70%. Apoptotic cells may acquire serum CRP, a known classical complement pathway activator. It was observed that scFv(QuVHVL) blocked C1 binding to CRP and blocked CRP-mediated classical pathway activation using an ELISA format. However, under the experimental conditions used, the addition of exogenous CRP to apoptotic cells did not further increase the levels of C4b, C3b, or MAC deposition significantly, suggesting predominance by other activation mechanisms, such as antibody-C1-mediated complement activation. In summary, the results indicated that C1-mediated classical pathway activation was a highly significant mechanism for complement activation by apoptotic cells. In the future, specific inhibition of classical complement pathway activation by a humanized form of scFv(QuVHVL) may be useful in reducing inadvertent damage to healthy bystander tissue in a variety of acute, complement-mediated inflammatory conditions, including ischemia/reperfusion injury.
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PMID:Specific inhibition of the classical complement pathway with an engineered single-chain Fv to C1q globular heads decreases complement activation by apoptotic cells. 1958 84

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