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

The purpose of this study was to investigate whether propofol has a neuroprotective effect on the fetal brain after intrauterine ischemia-reperfusion (I/R) injury in the rat fetus. Fetal brain ischemia was induced by clamping the utero-ovarian artery bilaterally for 30 min and reperfusion was achieved by removing the clamps for 2 h. A 40-mg/kg single dose of propofol was administered intraperitoneally 15 min before I/R injury. Lipid peroxidation in the brain tissue was determined as the concentration of thiobarbituric acid reactive substances (TBARS) for each fetal rat. Results showed that lipid peroxidation byproducts increased after I/R injury. Maternal treatment with propofol reduced TBARS compared to the I/R group. Propofol has been shown to have neuroprotective effects in intrauterine I/R-induced fetal brain damage in rats.
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PMID:Maternal treatment with propofol attenuates lipid peroxidation after transient intrauterine ischemia in the neonatal rat brain. 1470 28

The neuroprotective potency of anesthetics such as propofol compared to mild hypothermia remains undefined. Therefore, we determined whether propofol at two clinically relevant concentrations is as effective as mild hypothermia in preventing delayed neuron death in hippocampal slice cultures (HSC). Survival of neurons was assessed 2 and 3 days after 1 h oxygen and glucose deprivation (OGD) either at 37 degrees C (with or without 10 or 100 microM propofol) or at an average temperature of 35 degrees C during OGD (mild hypothermia). Cell death in CA1, CA3, and dentate neurons in each slice was measured with propidium iodide fluorescence. Mild hypothermia eliminated death in CA1, CA3, and dentate neurons but propofol protected dentate neurons only at a concentration of 10 microM; the more ischemia vulnerable CA1 and CA3 neurons were not protected by either 10 microM or 100 microM propofol. In slice cultures, the toxicity of 100 muM N-methyl-D-aspartate (NMDA), 500 microM glutamate, and 20 microM alpha-amino-5-methyl-4-isoxazole propionic acid (AMPA) was not reduced by 100 microM propofol. Because propofol neuroprotection may involve gamma-aminobutyric acid (GABA)-mediated indirect inhibition of glutamate receptors (GluRs), the effects of propofol on GluR activity (calcium influx induced by GluR agonists) were studied in CA1 neurons in HSC, in isolated CA1 neurons, and in cortical brain slices. Propofol (100 and 200 microM, approximate burst suppression concentrations) decreased glutamate-mediated [Ca2+]i increases (Delta[Ca2+]i) responses by 25%-35% in isolated CA1 neurons and reduced glutamate and NMDA Delta[Ca2+]i in acute and cultured hippocampal slices by 35%-50%. In both CA1 neurons and cortical slices, blocking GABAA receptors with picrotoxin reduced the inhibition of GluRs substantially. We conclude that mild hypothermia, but not propofol, protects CA1 and CA3 neurons in hippocampal slice cultures subjected to oxygen and glucose deprivation. Propofol was not neuroprotective at concentrations that reduce glutamate and NMDA receptor responses in cortical and hippocampal neurons.
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PMID:Mild hypothermia, but not propofol, is neuroprotective in organotypic hippocampal cultures. 1561 81

Lung dysfunction after cardiopulmonary bypass and lung transplantation results from oxidant-mediated cellular damage. Previously, we observed the shedding of angiotensin-converting enzyme (ACE) from the endothelial cell surface to be a more sensitive and earlier marker of oxidative lung endothelial injury than lung wet-to-dry weight ratio. The aim of this study was to evaluate the potential of the anesthetic propofol, which has antioxidant properties, to prevent oxidative lung injury by measuring ACE shedding. ACE release from isolated perfused rat lungs increased significantly after ischemia-reperfusion (I/R). Propofol significantly decreased I/R-induced ACE release by 23.4% (P < 0.05). Perfusion with 0.75 mM H(2)O(2) also caused ACE release from the lung microvasculature, which was similarly attenuated by propofol. The protective effect of propofol on H(2)O(2)-induced ACE shedding was confirmed in vitro using Chinese Hamster Ovary cells overexpressing human ACE. Thus, propofol can attenuate oxidative injury of the pulmonary endothelium as detected by ACE shedding in I/R and H(2)O(2) models of acute lung injury.
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PMID:Propofol attenuates lung endothelial injury induced by ischemia-reperfusion and oxidative stress. 1578

The general anesthetic propofol has been shown to be cardioprotective. However, its benefits when used in cardioplegia during cardiac surgery have not been demonstrated. In this study, we investigated the effects of propofol on metabolic stress, cardiac function, and injury in a clinically relevant model of normothermic cardioplegic arrest and cardiopulmonary bypass. Twenty anesthetized pigs, randomized to propofol treatment (n = 8) and control (n = 12) groups, were surgically prepared for cardiopulmonary bypass (CPB) and cardioplegic arrest. Doses of warm blood cardioplegia were delivered at 15-min intervals during a 60-min aortic cross-clamped period. Propofol was continuously infused for the duration of CPB and was therefore present in blood cardioplegia. Myocardial biopsies were collected before, at the end of cardioplegic arrest, and 20 mins after the release of the aortic cross-clamp. Hemodynamic parameters were monitored and blood samples collected for cardiac troponin I measurements. Propofol infusion during CPB and before ischemia did not alter cardiac function or myocardial metabolism. Propofol treatment attenuated the changes in myocardial tissue levels of adenine nucleotides, lactate, and amino acids during ischemia and reduced cardiac troponin I release on reperfusion. Propofol treatment reduced measurable hemodynamic dysfunction after cardioplegic arrest when compared to untreated controls. In conclusion, propofol protects the heart from ischemia-reperfusion injury in a clinically relevant experimental model. Propofol may therefore be a useful adjunct to cardioplegic solutions as well as being an appropriate anesthetic for cardiac surgery.
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PMID:Propofol is cardioprotective in a clinically relevant model of normothermic blood cardioplegic arrest and cardiopulmonary bypass. 1595 71

Patients with heart failure have a diminished cardiac reserve capacity that may be further compromised by anesthesia. In addition to depression of sympathetic activity, most anaesthetics interfere with cardiovascular performance, either by a direct myocardial depression or by modifying cardiovascular control mechanisms. Etomidate causes the least cardiovascular depression. It is popular for induction of anesthesia in cardiac-compromised patients; however, it is not suitable for maintenance of anesthesia because it depresses adrenocortical function. Ketamine has a favorable cardiovascular profile related to central sympathetic stimulation and inhibition of neuronal catecholamine uptake. These counteract its direct negative inotropic effect. In patients with a failing myocardium, however, the negative inotropic effects may be unmasked, resulting in deterioration in cardiac performance and cardiovascular instability. Propofol is the most popular intravenous anesthetic for maintenance of anesthesia. It does have a negative inotropic effect, but the net effect on myocardial contractility is insignificant at clinical concentrations, probably because of a simultaneous increase in the sensitivity of the myofilaments to Ca2+. Propofol protects the myocardium against ischemia-reperfusion injury, an action derived from its antioxidant and free-radical-scavenging properties as well as the related inhibition of the mitochondrial permeability transition pore. For intravenous anesthesia, propofol is always combined with an opioid. Opioids have relatively few cardiovascular side effects and, in particular, do not cause myocardial depression. Indeed, they are cardioprotective, with antiarrhythmic activity, and induce pharmacologic preconditioning of the myocardium by a mechanism similar to the inhalational anesthetics.
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PMID:Intravenous anesthesia for the patient with left ventricular dysfunction. 1670 33

Intravenous regional anesthesia (IVRA) is a technique whereby a tourniquet is used to restrict blood flow to an exsanguinated limb. Propofol was shown to attenuate ischemia-reperfusion damage. We aimed to investigate the effect of low-dose propofol as an antioxidant in this process. Twenty-six unpremedicated adult patients (ASA I-II) were studied. The patients in the control group (Group C, n = 12) were administered 40 ml of 0.5% lidocaine, while the patients in the propofol group (Group P, n = 14) were administered 40 ml of 0.5% lidocaine plus 20 mg propofol for IVRA. Serum levels of malondialdehyde (MDA) and paraoxonase activity were measured at 1 min before, immediately upon, and 30 min after the release of the tourniquet. Serum paraoxonase activity was observed to have a significant decreasing course in both groups (p < 0.01). In contrast, we observed a progressive increase in the serum levels of MDA in Group C (p < 0.05). However, in Group P, serum levels of MDA after the release of the tourniquet periods were significantly lower than that before the release of the tourniquet (p < 0.05). The addition of propofol (20 mg) to lidocaine for IVRA inhibits MDA levels. We conclude that the addition of propofol to lidocaine can be considered as a useful antioxidant in this type of anesthesia.
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PMID:The effect of propofol as an antioxidant agent in intravenous regional anesthesia. 1713 32

To demonstrate a direct protective effect of propofol on myocardial contractile performance during an ischemic episode and investigate underlying mechanisms, isolated adult rat ventricular cardiomyocytes were subjected for 2 h to (i) ischemic medium containing 2-deoxyglucose (20 mM), gassed with 100% N(2) at pH 6.4, (ii) normal medium with 95% O(2)/5% CO(2) at pH 7.4 or (iii) normal medium with addition of H(2)O(2) (50 microM). Propofol under normal conditions decreased the peak amplitude of electrically stimulated contraction of cardiomyocytes from a basal value of 6.5+/-0.37 microm to a maximum attenuation ( approximately 37%) at 0.44 to 56 microM. Under ischemic conditions, the contraction amplitude at baseline was 2.8+/-0.34 microm, but propofol, despite having a cardiodepressant effect per se, stimulated contraction, such that at >or=0.44 microM, normal and ischemic values in the presence of propofol were similar. Comparably, pro-oxidant (H(2)O(2))-induced attenuation of cell shortening was reversed by propofol (0.5 microM) to the level of contractile activity produced by the anaesthetic alone. The protective effect against ischemia-induced injury was not reflected in an improved ATP/ADP ratio nor was it mediated through diltiazem-sensitive L-type Ca(2+) channels. Propofol (0.5 microM) did, however, attenuate the ischemia- and H(2)O(2)-induced increases in the membrane lipid hydroperoxides, MDA (by 83% and 30%) and 4-HNE (by 47% and 69%). It is concluded that propofol, at clinically relevant concentrations, can counteract the effects of increased production of free radical compounds by cardiomyocytes subjected to oxidant stress and improve contractile performance.
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PMID:Protection of cardiomyocyte function by propofol during simulated ischemia is associated with a direct action to reduce pro-oxidant activity. 1732 10

Propofol (2,6-diisopropylphenol) is a versatile, short-acting, intravenous (i.v.) sedative-hypnotic agent initially marketed as an anesthetic, and now also widely used for the sedation of patients in the intensive care unit (ICU). At the room temperature propofol is an oil and is insoluble in water. It has a remarkable safety profile. Its most common side effects are dose-dependent hypotension and cardiorespiratory depression. Propofol is a global central nervous system (CNS) depressant. It activates gamma-aminobutyric acid (GABA A) receptors directly, inhibits the N-methyl-d-aspartate (NMDA) receptor and modulates calcium influx through slow calcium-ion channels. Furthermore, at doses that do not produce sedation, propofol has an anxiolytic effect. It has also immunomodulatory activity, and may, therefore, diminish the systemic inflammatory response believed to be responsible for organ dysfunction. Propofol has been reported to have neuroprotective effects. It reduces cerebral blood flow and intracranial pressure (ICP), is a potent antioxidant, and has anti-inflammatory properties. Laboratory investigations revealed that it might also protect brain from ischemic injury. Propofol formulations contain either disodium edetate (EDTA) or sodium metabisulfite, which have antibacterial and antifungal properties. EDTA is also a chelator of divalent ions such as calcium, magnesium, and zinc. Recently, EDTA has been reported to exert a neuroprotective effect itself by chelating surplus intracerebral zinc in an ischemia model. This article reviews the neuroprotective effects of propofol and its mechanism of action.
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PMID:The experimental and clinical pharmacology of propofol, an anesthetic agent with neuroprotective properties. 1848 23

There are numerous sedatives and analgesics used in critical care medicine today; these medications are used on critically ill patients, many of whom have heart disease, including coronary artery disease or congestive heart failure. The purpose of this review is to recognize the effects of these medications on the heart. Studies that evaluated the effects of sedatives and analgesics on normal individuals or on those with heart disease were reviewed. Current choices for sustained sedation in the critically ill include the benzodiazepines, morphine, propofol, and etomidate. Each of these medications has their particular advantages and disadvantages. Benzodiazepines provide the greatest amnesia and cardiovascular safety but they can cause significant hypotension in the hemodynamically unstable patient. Morphine provides analgesia and cardioprotective activity after ischemia, although the large observational study CRUSADE showed increased mortality rate in those patients with non-ST segment elevation myocardial infarction who received morphine. Propofol is the most easily titratable drug with cardioprotective features, but its use must be accompanied with great attention to possible development of propofol infusion syndrome, which is a deadly disease, especially in patients with head injury and those with septic shock receiving vasopressors. Etomidate has a rapid onset effect and short period of action with great hemodynamic stability even in patients with shock and hypovolemia, but the incidence of adrenal insufficiency during infusion, not bolus doses, may cause deterioration in the circulatory stability. In conclusion, the sedatives and analgesics mentioned here have characteristics that give them a cardiovascular safety profile useful in critically ill patients. However, use of these drugs on an individual basis is dependent on each agent's safety and efficacy.
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PMID:Cardiovascular manifestations of sedatives and analgesics in the critical care unit. 1909 49

Cerebral ischemia is a major cause of death and disability and may be a complication of neurosurgery. Certain anesthetics may improve recovery after ischemia and hypoxia by altering electrophysiological changes during the insult. Intracellular recordings were made from CA1 pyramidal cells in hippocampal slices from adult rats. Desflurane or propofol was applied 10 min before and during 10 min of hypoxia (95% nitrogen, 5% carbon dioxide). None of the untreated CA1 pyramidal neurons, 46% of the 6% desflurane- and 38% of the 12% desflurane-treated neurons recovered their resting and action potentials 1 h after hypoxia (P<0.05). Desflurane (6% or 12%) enhanced the hypoxic hyperpolarization (4.9 or 4.7 vs. 2.6 mV), increased the time until the rapid depolarization (441 or 390 vs. 217 s) and reduced the level of depolarization at 10 min of hypoxia (-13.5 or -13.0 vs. -0.6 mV); these changes may be part of the mechanism of its protective effect. Either chelerythrine (5 microM), a protein kinase C inhibitor, or glybenclamide (5 microM), a K(ATP) channel blocker, prevented the protective effect and the electrophysiological changes with 6% desflurane. Propofol (33 or 120 microM) did not improve recovery (0 or 0% vs. 0%) 1 h after 10 min of hypoxia; it did not significantly enhance the hypoxic hyperpolarization (3.6 or 3.1 vs. 2.6 mV) or increase the latency of the rapid depolarization (282 or 257 vs. 217 s). The average depolarization at 10 m of hypoxia with 33 microM propofol (-4.1 mV) was slightly but significantly different from that in untreated hypoxic tissue (-0.6 mV). Desflurane but not propofol improved recovery of the resting and action potentials in hippocampal slices after hypoxia, this improvement correlated with enhanced hyperpolarization and attenuated depolarization of the membrane potential during hypoxia. Our results demonstrate differential effects of anesthetics on electrophysiological changes during hypoxia.
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PMID:Effects of desflurane and propofol on electrophysiological parameters during and recovery after hypoxia in rat hippocampal slice CA1 pyramidal cells. 1923 6


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