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

Elevated intracellular calcium (iCa2+) plays an important role in the pathophysiology of ischemic brain damage. The mechanisms by which iCa2+ increases are uncertain. Recent evidence implicates the voltage-dependent calcium channel (VDCC) as a likely site for the alteration in Ca2+ homeostasis during ischemia. The purpose of this study was to determine whether VDCCs are altered by global ischemia and reperfusion in a canine cardiac arrest, resuscitation model. We employed the radioligand, [3H]PN200-110, to quantitate the equilibrium binding characteristics of the VDCCs in the cerebral cortex. Twenty-five adult beagles were separated into four experimental groups: (a) nonischemic controls, (b) those undergoing 10-min ventricular fibrillation and apnea, (c) those undergoing 10-min ventricular fibrillation and apnea followed by spontaneous circulation and controlled respiration for 2 and (d) 24 h. Brain cortex samples were taken prior to killing of the animal, frozen immediately in liquid nitrogen, and crude synaptosomal membranes isolated by differential centrifugation/filtration. After 10 min of ischemia the maximal binding (Bmax) of [3H]PN200-110 increased to greater than 250% of control values (control Bmax 11.16 +/- 0.98; ischemic 28.35 +/- 2.78 fmol/mg protein; p less than 0.05). Bmax returned to near control values after 2 h of reperfusion but remained significantly greater than the control at 24 h. Although the affinity constant (Kd) (control = 0.12 +/- 0.03 nM) appeared to increase with ischemia and normalize with reperfusion, the changes were not statistically significant. We conclude that the binding of [3H]PN200-110 to L-type VDCCs is increased after 10 min of global ischemia/anoxia produced by ventricular fibrillation and apnea in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alteration of voltage-dependent calcium channels in canine brain during global ischemia and reperfusion. 131 42

Renal function and morphology were studied before and after 60 min of renal ischemia and contralateral nephrectomy in two groups of rabbits. The animals were pretreated with ginsenosides (n = 22) and saline (n = 22) respectively, the latter as control. Results showed that ginsenosides (30 mg/kg body wt.) pretreatment by intravenous injection 10 min before warm ischemia resulted in the survival of all the animals with better renal function, 1, 3 and 7 days after blood urea nitrogen, fraction of excreted sodium and urine protein were observed in the control rabbits and a less pronounced increase was noted (P less than 0.05) after pretreatment with ginsenosides. The appearance of kidney tissue taken from surviving rabbits with Ginsenosides pretreatment was found to be normal under light microscope. Severe tubular necrosis was observed in kidneys of the control group. Tissues were examined with a transmission electron microscope. ginsenosides have protective effects on the epithelial cells of the proximal convoluted tubules, and microvilli and mitochondria were less damaged by ischemia than those of the control animals. There was also a large amount of ribosome on rough surfaced endoplasmic reticulum in the cells of ginsenosides-treated kidney, reflecting their ability to stimulate ribonucleic acid and protein synthesis. This is considered to be the basis of improvement of renal function.
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PMID:[Protective effects of ginsenosides on warm ischemic damages of the rabbit kidney]. 132 38

Peroxynitrite (ONOO-), the reaction product of superoxide (O2-) and nitric oxide (NO), may be a major cytotoxic agent produced during inflammation, sepsis, and ischemia/reperfusion. Bovine Cu,Zn superoxide dismutase reacted with peroxynitrite to form a stable yellow protein-bound adduct identified as nitrotyrosine. The uv-visible spectrum of the peroxynitrite-modified superoxide dismutase was highly pH dependent, exhibiting a peak at 438 nm at alkaline pH that shifts to 356 nm at acidic pH. An equivalent uv-visible spectrum was obtained by Cu,Zn superoxide dismutase treated with tetranitromethane. The Raman spectrum of authentic nitrotyrosine was contained in the spectrum of peroxynitrite-modified Cu,Zn superoxide dismutase. The reaction was specific for peroxynitrite because no significant amounts of nitrotyrosine were formed with nitric oxide (NO), nitrogen dioxide (NO2), nitrite (NO2-), or nitrate (NO3-). Removal of the copper from the Cu,Zn superoxide dismutase prevented formation of nitrotyrosine by peroxynitrite. The mechanism appears to involve peroxynitrite initially reacting with the active site copper to form an intermediate with the reactivity of nitronium ion (NO2+), which then nitrates tyrosine on a second molecule of superoxide dismutase. In the absence of exogenous phenolics, the rate of nitration of tyrosine followed second-order kinetics with respect to Cu,Zn superoxide dismutase concentration, proceeding at a rate of 1.0 +/- 0.1 M-1.s-1. Peroxynitrite-mediated nitration of tyrosine was also observed with the Mn and Fe superoxide dismutases as well as other copper-containing proteins.
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PMID:Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. 141 74

The aim of this work was to assess the catalytic activity of xanthine oxidase, the level of lipid peroxides and enzymic antioxidant systems in isolated rat heart muscle subjected to a globally partial ischemia followed by varying durations of reperfusion. After 40 min of globally partial ischemia (residual perfusion flow rate: 0.1 ml/min), four different durations of reperfusion were investigated (0, 20, 40, and 60 min). After each experimental ischemia/reperfusion sequence, the heart was frozen in liquid nitrogen. Lipid peroxides were assayed in the cardiac homogenate and the catalytic activity of xanthine oxidase and enzymic antioxidant systems (glutathione peroxidase, superoxide dismutase and catalase) were determined in the centrifuged supernatant. In the different experimental protocols studied in this work, there was no significant increase in the activity of cardiac xanthine oxidase or in the level of lipid peroxides when compared to the non reperfused or to the continuously perfused hearts. Indeed, enzymic antioxidant systems were also not significantly modified in the different periods of reperfusion when compared to control hearts (continuously perfused hearts). These results suggest that xanthine oxidase is apparently not a major source of free radicals in the course of an ischemia-reperfusion sequence in heart muscle, in particular, if we consider the early phases of reperfusion. The process of lipid peroxidation, assessed by assaying thiobarbituric acid reactants, is not a predominant phenomenon of reperfusion-induced injury, at least in the experimental model used here. However, enzymic antioxidant systems investigated in this study do not seem modified. This could mean that the small quantity of oxygen free radicals produced does not overwhelm the enzymic antioxidant systems of myocardium which is in agreement with peroxidatized lipid results.
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PMID:Ischemia and reperfusion injury in isolated rat heart: effect of reperfusion duration on xanthine oxidase, lipid peroxidation, and enzyme antioxidant systems in myocardium. 146 31

Although a role for free radicals in myocardial damage during cardiopulmonary bypass for open heart surgery has been postulated, direct evidence of free radical production as well as consumption of tissue antioxidants such as vitamin E is still lacking. Twenty patients (age 26-66 yr, mean 48) undergoing elective open heart surgery with moderate hypothermia, and cold crystalloid cardioplegia, were studied. Cardiopulmonary bypass time was 61.4 +/- 31.2 min. The specimens of atrial tissue collection before and after cardiopulmonary bypass, were immediately frozen in liquid nitrogen. Mean vitamin E atrial content, measured by reverse phase HPLC, was 355 +/- 249 pmol/mg of dry weight basally, 135 +/- 85 pmol/mg (p < 0.05) at the end of the ischemic period and 405 +/- 288 pmol/mg after the reperfusion period (p < 0.01). Microscopic examination of right atrial biopsies ruled out differences in fibrosis or cellular damage as the cause of vitamin E changes. Although a great basal variability in atrial vitamin E content was observed, which was independent of age, sex and clinical status, a reproducible and substantial decrease in atrial vitamin E content after cardiopulmonary bypass occurred (mean reduction 45 +/- 17% and 55 +/- 22%, respectively, after ischemia and after reperfusion). This was directly related to the aorta cross-clamping duration and partially to the minimum temperature achieved. In conclusion, apart from the great variability observed in basal vitamin E tissue content, vitamin E was always reduced during cardiopulmonary bypass, suggesting an oxidative stress on the myocardium during open heart surgery.
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PMID:Myocardial vitamin E is consumed during cardiopulmonary bypass: indirect evidence of free radical generation in human ischemic heart. 146 17

Recent work has shown that dihydropyridine-type calcium channel blockers such as nitrendipine protect against ischemic liver damage in the rat in vivo (Thurman RG, Apel E and Lemasters JJ, J Cardiovasc Pharmacol 12: S113-S116, 1988), suggesting that calcium antagonists may have clinical value in preventing ischemic and hypoxic hepatic injury. This study was designed to examine the effects of two benzothiazepine-type calcium channel blockers, diltiazem and TA3090, in the hypoxic perfused rat liver. Livers were isolated and perfused briefly with oxygen-saturated buffer, followed by perfusion for 80 min with nitrogen-saturated buffer with diltiazem or TA3090 (20-200 microM), and concluding with 20 min of perfusion with oxygen-saturated buffer. In control preparations, maximal lactate dehydrogenase (LDH) release into effluent perfusate following hypoxia averaged about 1100 U/L. Diltiazem and TA3090 decreased LDH release at all concentrations studied; both drugs were most effective at the 100 microM concentration (71 and 73% inhibition, respectively). Oxygen uptake by control livers decreased 78% following hypoxia; diltiazem and TA3090 reduced this effect markedly, with maximal effectiveness again observed with 100 microM (O2 uptake was decreased by 22% with 100 microM diltiazem and by only 9% with 100 microM TA3090). Histological examination for nuclear uptake of the vital dye trypan blue revealed necrosis of parenchymal cells along with cell shrinking and consequent expansion of the sinusoids in control livers. Perfusion with diltiazem markedly reduced parenchymal cell death but did not alter the pattern of cell damage observed. In contrast, livers perfused with TA3090 during hypoxia had virtually no parenchymal cell damage, although moderate damage to nonparenchymal cells in the sinusoids occurred. The difference in mechanisms responsible for the phenomena which occur with diltiazem and TA3090 is not completely understood; however, these and other calcium antagonists clearly have powerful hepatoprotective effects against ischemia and hypoxia.
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PMID:Protective effects of the calcium antagonists diltiazem and TA3090 against hepatic injury due to hypoxia. 147 86

The effect of hypoxia on the incorporation of [14C]serine into serine glycerophospholipids was investigated in rat brain cortex. Brain slices were incubated, in the presence of the labeled precursor, in Krebs-Henseleit Ringer bicarbonate or Krebs Ringer phosphate, and hypoxia was induced by bubbling nitrogen in the medium. The lowering of oxygen caused an increase of the incorporation of the base into phosphatidylserine in slices incubated in both media, although the effect was greater in Krebs Ringer phosphate. Such an effect was also observed in the homogenate subjected to N2-treatment, with an increase in the incorporation similar to that obtained in slices incubated in Krebs-Henseleit Ringer bicarbonate. Phosphatidylserine is synthesized in mammalian tissues by a "base-exchange" enzyme, strictly Ca2+ dependent, and, moreover, is necessary for protein kinase C activity. We postulate that the increased synthesis of phosphatidylserine might affect signal transduction mechanisms and participate in the modification of lipid metabolism observed in hypoxia and/or ischemia.
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PMID:Serine incorporation into phosphatidylserine in hypoxic rat brain cortex. 149 81

Current forms of brain monitoring, such as electroencephalography (EEG), have had limited clinical utility. The EEG records spontaneous cerebrocortical activity and thus is an indirect indicator of metabolic demand and, to a lesser extent, an indicator of mismatch of supply versus demand. Ischemia modulates EEG activity in ways that can usually be detected, but EEG patterns can be similarly modulated by many other factors, including temperature and pharmacologic manipulation. This in vivo study in physiologically monitored animals evaluated the use of correlated optical spectroscopy, performed with an instrument having a fiberoptic light-guide bundle in contact with the cerebral cortex, for the simultaneous monitoring of cerebrovascular oxygen availability and intracellular oxygen delivery. A highly specific monitor of cerebral intracellular oxygen supply, the cerebrocortical intramitochondrial NADH redox state, was monitored in vivo with a fluorescence technique. Absorption spectroscopy was used concurrently to monitor hemoglobin content (blood volume) and oxygen saturation in the microcirculation. Correlated changes in optical signals from cerebrocortical NADH and hemoglobin were studied in a swine model (n = 7) of nitrogen hypoxia. Measurements were made at four wavelengths with a time-division, multiplexed fluorometer/reflectometer. Because the NADH fluorescence signal at 450 nm is affected by local changes in blood volume, a "corrected" fluorescence signal is usually calculated. In previous studies, where only two wave lengths have been measured, attempts at correction were based on reflectance at the excitation wavelength (366 nm). We compared estimators of changes in microcirculatory blood volume using reflection at two wavelengths: 366 nm and 585 nm, the wavelengths for maximum and isobestic absorption. The results of the studies were as follows: (1) during transient hypoxia, NADH and local hemoglobin saturation signals changed in concert with arterial pulse oximetry, with changes in NADH lagging behind changes in saturation by an average of 5.3 seconds; (2) after hypocapnic ventilation to a mean PaCO2 of 20.2 +/- 0.8 mm Hg, NADH increased by 11.5 +/- 8.7% (as compared with maximal change during anoxia), local hemoglobin saturation decreased by 7.7 +/- 6.4%, and local blood volume decreased by 12.5 +/- 13%, while arterial SpO2 was unchanged; (3) our two measures of local blood volume were closely correlated during carbon dioxide perturbations, but poorly correlated during hypoxic perturbation; and (4) NADH fluorescence provided a more rapid, sensitive indicator of oxygen deprivation than did the EEG. During transient hypoxia, EEG changes occurred 57.4 +/- 10.4 seconds after the onset of decline in local hemoglobin saturation, after NADH had completed 50% of its maximal increase.
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PMID:Correlated, simultaneous, multiple-wavelength optical monitoring in vivo of localized cerebrocortical NADH and brain microvessel hemoglobin oxygen saturation. 149 28

The purpose of this investigation was to characterize the effects of nitrous oxide or nitrogen (70%) on systemic and regional hemodynamics and myocardial tissue perfusion after a brief coronary artery occlusion (15 min) and reperfusion (3 h). Two groups of experiments (14 experiments total) were completed with 24 open-chest, barbiturate-anesthetized dogs. Coronary collateral blood flow was diverted from the ischemic zone during coronary artery occlusion to eliminate a source of variability in degree of ischemia produced by differences in degrees of collateral blood flow among animals. Seven of 16 dogs treated with nitrous oxide and 7 of 8 dogs treated with nitrogen survived coronary occlusion and reperfusion (P less than 0.05). Coronary artery occlusion produced paradoxical systolic bulging in the ischemic zone in both groups of experiments. After reperfusion, segment shortening gradually returned toward control levels but remained depressed from the preocclusion state after 3 h in the nitrogen-treated control group. Similar results were observed after reperfusion in the nitrous oxide group; however, segment function in the ischemic region was significantly (P less than 0.05) depressed throughout the 3-h reperfusion period compared with the control group. Transmural coronary collateral blood flow during occlusion was not significantly different (P greater than 0.05) between groups, indicating that differences in recovery of contractile function observed between groups could not be attributed to differences in myocardial oxygen supply. In addition, the similarity in systemic hemodynamics between the nitrous oxide and control groups indirectly suggests that differences in recovery of function could not be attributed to differences in myocardial oxygen demand. The results indicate that 70% nitrous oxide produces greater mortality after coronary artery occlusion and reperfusion and reduces functional recovery of post-ischemic, reperfused myocardium compared with 70% nitrogen in open-chest, acutely instrumented dogs.
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PMID:Nitrous oxide impairs functional recovery of stunned myocardium in barbiturate-anesthetized, acutely instrumented dogs. 153 Jan 67

Experiments in adult animals have indicated that hyperglycemia accentuates whereas hypoglycemia ameliorates hypoxic-ischemic brain damage. To determine whether hypoglycemia is protective or deleterious to the perinatal brain subjected to hypoxia-ischemia, 7-d postnatal rats were rendered hypoglycemic either by receiving an s.c. injection of insulin or fasting for 12 h. All rat pups underwent unilateral common carotid artery ligation followed by exposure to 8% oxygen-balance nitrogen at 37 degrees C for 2 h. Control animals (no insulin or fasting) received s.c. injections of normal saline. Mean blood glucose concentrations were 5.4 +/- 0.1, 4.3 +/- 0.2, and 3.4 +/- 0.1 mmol/L for control, insulin, and fasted animals, respectively. Blood beta-hydroxybutyrate concentrations were identical (0.5 +/- 0.1 mmol/L) for control and insulin-treated animals, but more than doubled in concentration in the fasted animals (p less than 0.001). Mortality rates during hypoxia-ischemia were higher in the insulin-treated animals (30%) than in either the fasted (4%) or control (0%) animals (p less than 0.05). Fasted animals showed a significant reduction in hypoxic-ischemic brain damage as compared with either the insulin-treated or control animals. Insulin-treated animals were not significantly different from controls. The findings indicate that 1) insulin induced hypoglycemia does not provide a protective effect on perinatal hypoxic-ischemic brain damage, as in adults; and 2) fasting adequate to produce hypoglycemia and ketonemia improved neuropathologic outcome.
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PMID:Effect of insulin-induced and fasting hypoglycemia on perinatal hypoxic-ischemic brain damage. 154 41


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