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

One of the ulcerogenic mechanisms by which ethanol induces mucosal lesions in the stomach is the depression of gastric mucosal blood flow (GMBF). The goal of this study was to determine whether lesion formation is the result of vascular ischemia alone or ischemia combined with congestion. The aims of this study were to answer this question by evaluating the relationship between GMBF, oxygen saturation (ISO2) and hemoglobin volume (IHb) in the gastric mucosa under the influences of ethanol and prostaglandin E2 (PGE2) in the ischemic and congestive states, using a laser Doppler flowmeter and tissue spectrum analyzer. Ligation of the gastric celiac artery or vein markedly decreased the GMBF and the ISO2 level. The former procedure also reduced but the latter increased the IHb level. Ethanol administration produced effects similar to venous ligation, i.e. vascular stasis with ischemia. There was a negative correlation between GMBF and severity of lesion formation after ethanol administration. However, at the lesion site all the hemodynamic parameters were significantly reduced, indicating that a necrotic condition had occurred. PGE2 preincubation (25 micrograms) elevated GMBF, ISO2 and IHb levels. It also alleviated the reduction of blood flow induced by ethanol and increased the recovery rate of GMBF and ISO2 after the release of arterial or venous ligation. It is concluded that the decrease in blood flow due to ethanol is probably caused by constriction of venules rather than arterioles inside the mucosa, and this effect could lead to vascular congestion. PGE2 probably dilates both arterioles and venules in the gastric mucosa and thereby increases the blood flow in the gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Assessment of hemodynamic changes in rat stomachs by laser Doppler velocimetry and reflectance spectrophotometry. Effects of ethanol and prostaglandin E2 under ischemic and congestive conditions. 770 51

Reactive oxygen metabolites may be involved in the pathogenesis of ethanol-, nonsteroidal antiinflammatory drug-, Helicobacter pylori-, or ischemia/reoxygenation-induced gastric mucosal injury in vivo. Iron plays a critical role in mediating oxidant injury in vitro. The present study examined a possible role of lipid peroxidation in inducing oxidant damage by determining the effect of iron chelation on cytotoxicity and on lipid peroxidation in cultured rat gastric cells. Cytotoxicity was quantified by 51Cr release from prelabeled cells that were exposed to tert-butyl hydroperoxide (tBHP) so as to overwhelm the glutathione redox cycle. Lipid peroxidation was assessed by measuring malondialdehyde (MDA) production. tBHP caused a time-related and dose-dependent increase of 51Cr release. The presence of phenanthroline (a chelator of Fe2+) during tBHP exposure and pretreatment with deferoxamine (a chelator of Fe3+) reduced tBHP-induced 51Cr release dose dependently. The generation of MDA increased as the concentrations of tBHP increased, but in a time course study, such generation preceded cytolysis. Both iron chelators attenuated MDA production in a dose-dependent fashion. Oxidant stress causes lipid peroxidation in cultured gastric cells, which is then followed by cytolysis. Iron plays a critical role in inducing lipid peroxidation as well as in mediating cytolysis. Iron chelation protects these cells from oxidant stress presumably through inhibition of lipid peroxidation.
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PMID:Protection of cultured rat gastric cells against oxidant stress by iron chelation. Role of lipid peroxidation. 772 Apr 85

Neutrophils have been identified to play a major role in ischemia/reperfusion injury through several mechanisms. Neutrophil migration into reperfused gut may reduce bacterial translocation, but may also enhance the reperfusion injury. Ethanol ingestion impairs cutaneous chemotaxis, but its effects on neutrophil migration to postischemic small bowel are unknown. This study investigates the effects of ethanol on small bowel accumulation of neutrophils after ischemia/reperfusion. Ninety-five rats were divided into five groups; normal control, sham operation, ethanol-sham, ischemia, and ethanol-ischemia groups. Ethanol was given once acutely by gavage (3 g/kg, 20% solution) to the animals in the ethanol-sham and the ethanol-ischemia groups 4 hr before ischemic injury. Ischemia was produced for 1 hr by placing a vessel loop around the superior mesenteric vessels. After 1 hr, 87% of animals had gut ischemia and the loop was removed. Three hours later the small bowel was examined for necrosis and the reperfused viable small bowel was extirpated for measurement of neutrophil infiltration by colorimetric assay for myeloperoxidase (MPO), an enzyme restricted to neutrophils. Both ethanol and ischemia/reperfusion produced significant independent increase in the MPO activity. When ethanol was given prior to ischemia, the MPO activity was further increased by statistically significant margin. The present study demonstrated that ethanol enhanced the effects of gut ischemia/reperfusion injury on PMN accumulation into the intestinal wall. These observations suggest that ethanol may potentiate ischemic injury to the gut and lead to increased problems when gut blood flow is significantly impaired.
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PMID:Ethanol ingestion potentiates PMN migration into small intestine after ischemia. 772 15

Gram-negative sepsis as well as administration of agents that simulate or occur naturally subsequent to a septic challenge, can present as an oxidant stress to the myocardium. These stresses may then induce the development of protection of the heart from future stresses. This protection of the heart may occur in spite of the fact that sepsis itself induces myocardial dysfunction. In the present study we determined if sepsis is protective of a 50 min ischemic episode, one in which some degree of irreversible damage may occur. In addition we determined if sepsis-induced protection was still present when this ischemic challenge was imposed upon the heart of the alcoholic septic animal in which the chronic alcoholic state can lead to a potentiation of sepsis induced cardiac depression. Thus animals were fed an ethanol containing diet or a control diet for 8-10 weeks and were then made septic by the administration of Escherichia coli into the dorsal subcutaneous space. Control animals received sterile saline. The following day, hearts were studied in the isovolumic beating preparation and, after basal function was assessed, hearts were made globally ischemic for 50 min and reperfused for 30 min. Left ventricular pressure was continuously monitored and coronary flow was measured at specific intervals. After ischemia and reperfusion, hearts from control- and alcohol-fed animals that were nonseptic showed significantly decreased left ventricular performance. Ventricular pressure development of hearts from septic and alcoholic septic rats was not significantly decreased after ischemia and reperfusion compared to preischemia although preischemic function was significantly lower in the sepsis groups compared to their nonseptic control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of sepsis on recovery of the heart from 50 min ischemia. 773 72

Cerebral ischemia in the gerbil results in early hippocampal changes, which include transient activation and/or translocation of protein kinase C (PKC), increased enzymatic activity of ornithine decarboxylase (ODC), and elevated DNA binding ability of activator protein-1 (AP1). The time-course of all three of these postischemic responses was found to be almost parallel, peaking at 3 hr after the ischemic insult. The effectiveness of known modulators of postischemic morphological outcome (MK-801, L-NAME, and gingkolides BN 52020 and BN 52021) in counteracting the induction of PKC, ODC, and AP1 formation was tested. These drugs were administrated as followed: MK-801 (a noncompetitive inhibitor of NMDA channel), 0.8 mg/kg i.p., 30 min before ischemia, and 5 min after the insult; L-NAME (competitive inhibitor of NO synthase), 10 mg/kg i.p., 30 min before ischemia, and 5 mg/kg, 5 min after ischemia; BN52020 and BN52021 (inhibitors of platelet-activating factor: PAF receptors) were administered as a suspension in 5% ethanol in water by oral route, 10 mg/kg for 3 days before ischemia. Three of these drugs, MK-801, L-NAME, and BN52021, significantly reduced ischemia-elevated activity of PKC and ODC, whereas AP1 formation was only partially attenuated. Our observations implicate the existence of different mechanism(s) for postischemic PKC and ODC activation, which in turn is engaged in AP1 induction.
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PMID:Modulation of ischemic signal by antagonists of N-methyl-D-aspartate, nitric oxide synthase, and platelet-activating factor in gerbil hippocampus. 774 16

Copper Fenton systems (Cu(II)/H2O2 and Cu(II)/Asc) inactivated the lipoamide reductase and enhanced the diaphorase activity of pig-heart lipoamide dehydrogenase (LADH). Cupric ions alone were less effective. As a result of Cu(II)/H2O2 treatment, the number of titrated thiols in LADH decreased from 6 to 1 per subunit. NADH and ADP (not NAD+ or ATP) enhanced LADH inactivation by Cu(II). NADH also enhanced the effect of Cu(II)/H2O2. Dihydrolipoamide, dihydrolipoic acid, Captopril, acetylcysteine, EDTA, DETAPAC, histidine, bathocuproine, GSSG and trypanothione prevented LADH inactivation. 100 microM GSH, DL-dithiothreitol, N-(2-mercaptopropionylglicine) and penicillamine protected LADH against Cu(II)/Asc and Cu(II), whereas 1.0 mm GSH and DL-dithiothreitol also protected LADH against Cu(II)/H2O2. Allopurinol provided partial protection against Cu(II)/H2O2. Ethanol, mannitol, Na benzoate and superoxide dismutase failed to prevent LADH inactivation by Cu(II)/H2O2 or Cu(II). Catalase (native or denaturated) and bovine serum albumin protected LADH but that protection should be due to Cu binding. LADH inhibited deoxyribose oxidation and benzoate hydroxylation by Cu(II)/H2O2. It is concluded that site-specifically generated HO, radicals were responsible for LADH inactivation by Cu(II) Fenton systems. The latter effect is discussed in the context of ischemia-reoxygenation myocardial injury.
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PMID:Inactivation of heart dihydrolipoamide dehydrogenase by copper Fenton systems. Effect of thiol compounds and metal chelators. 775

One hundred percent of anesthetized rats administered 6.6 gm/kg of ethanol IP died within 10-35 min of alcohol injection; upon autopsy of the brain all demonstrated profound subarachnoid and intracranial bleeding, clear signs of hemorrhagic stroke. Pretreatment of rats with 4 mumol/min MgCl2, but not saline, via IV administration (for 30-45 min), prevented hemorrhagic stroke in all animals so treated with 6.6 gm/kg ethanol. Administration of the stroke dose of alcohol resulted in rapid (within 3-5 min) and marked deficits in whole brain intracellular free Mg ([Mg2++]i) as observed by in vivo 31P-NMR spectroscopy. Intracellular pH (pHi) and the phosphocreatine [PCr]/[ATP] ratio also fell following a significant fall in brain [Mg2+]i). Brains of rats that exhibited strokelike events, upon death and autopsy, demonstrated continued and marked intracellular acidosis with progressive fall in the [PCr]/[ATP] ratio and elevation of inorganic phosphate (Pi) and [H+]i; these events were not accompanied by any rises in systemic arterial blood pressure. Rats pretreated with MgCl2 exhibited relatively stable brain [Mg2+]i, and essentially unchanged pHi, [PCr], [ATP], or [Pi] following alcohol administration, although such animals exhibited threefold alterations in plasma Mg2+, as measured by ion selective electrodes. These observations suggest that high alcohol ingestion can result in severe vasospasm, ischemia, and rupture of blood vessels probably as a consequence of depletion of brain [Mg2+]i, events that can be prevented by Mg2+ pretreatment.
Alcohol
PMID:Role of brain [Mg2+]i in alcohol-induced hemorrhagic stroke in a rat model: a 31P-NMR in vivo study. 777 64

It is not known why alcohol ingestion poses a risk for development of hypertension, stroke and sudden death. Of all drugs, which result in body depletion of magnesium (Mg), alcohol is now known to be the most notorious cause of Mg-wasting. Recent data obtained through the use of biophysical (and noninvasive) technology suggest that alcohol may induce hypertension, stroke, and sudden death via its effects on intracellular free Mg2+ ([Mg2+]i), which in turn alter cellular and subcellular bioenergetics and promote calcium ion (Ca2+) overload. Evidence is reviewed that demonstrates that the dietary intake of Mg modulates the hypertensive actions of alcohol. Experiments with intact rats indicates that chronic ethanol ingestion results in both structural and hemodynamic alterations in the microcirculation, which, in themselves, could account for increased vascular resistance. Chronic ethanol increases the reactivity of intact microvessels to vasoconstrictors and results in decreased reactivity to vasodilators. Chronic ethanol ingestion clearly results in vascular smooth muscle cells that exhibit a progressive increase in exchangeable and cellular Ca2+ concomitant with a progressive reduction in Mg content. Use of 31P-NMR spectroscopy coupled with optical-backscatter reflectance spectroscopy revealed that acute ethanol administration to rats results in dose-dependent deficits in phosphocreatine (PCr), the [PCr]/[ATP] ratio, intracellular pH (pHi), oxyhemoglobin, and the mitochondrial level of oxidized cytochrome oxidase aa3 concomitant with a rise in brain-blood volume and inorganic phosphate. Temporal studies performed in vivo, on the intact brain, indicate that [Mg2+]i is depleted before any of the bioenergetic changes. Pretreatment of animals with Mg2+ prevents ethanol from inducing stroke and prevents all of the adverse bioenergetic changes from taking place. Use of quantitative digital imaging microscopy, and mag-fura-2, on single-cultured canine cerebral vascular smooth muscle, human endothelial, and rat astrocyte cells reveals that alcohol induces rapid concentration-dependent depletion of [Mg2+]i. These cellular deficits in [Mg2+]i seem to precipitate cellular and subcellular disturbances in cytoplasmic and mitochondrial bioenergetic pathways leading to Ca2+ overload and ischemia. A role for ethanol-induced alterations in [Mg2+]i should also be considered in the well-known behavioral actions of alcohol.
Alcohol Clin Exp Res 1994 Oct
PMID:Role of magnesium and calcium in alcohol-induced hypertension and strokes as probed by in vivo television microscopy, digital image microscopy, optical spectroscopy, 31P-NMR, spectroscopy and a unique magnesium ion-selective electrode. 784 86

Evidence implicating leukocytes as mediators of tissue injury in different disease processes is accumulating rapidly. The sequestration and activation of neutrophils have been shown to be key components in the pathophysiology of chronic inflammatory bowel diseases, and in gastrointestinal lesions following hemorrhagic shock, ischemia-reperfusion, and ingestion of nonsteroidal anti-inflammatory drugs, or ethanol. Leukocyte-endothelial cell interactions also appear to be a target for the action of various drugs proven to be useful in the treatment of gastrointestinal inflammatory disorders. This review focuses on the alterations in leukocyte-endothelial cell interactions in the aforementioned conditions.
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PMID:Leukocyte-endothelial cell interactions: implications for the pathogenesis and treatment of gastrointestinal disease. 785 Oct 2

This study examined the effect of 1,3-butanediol on the selective loss of CA1 pyramidal neurons following a short period of near-complete forebrain ischemia. Injection of 55 mmol 1,3-butanediol/kg body weight at 24 h of recirculation and again at 36 h following 10 min of forebrain ischemia markedly reduced damage to CA1 neurons examined at 72 h of recirculation compared with that in saline-treated rats. Comparable treatment with ethanol did not cause significant protection. Neuronal loss was also not reduced by 1,3-butanediol treatment when the ischemic period was extended to 15 min or by single treatments at 24 h or 36 h following 10 min of ischemia. However, a single treatment 5 min after reversal of 10 min of ischemia was effective in ameliorating cell loss. The difference in effectiveness of 1,3-butanediol following 10 min and 15 min of ischemia is consistent with a number of previous studies, indicating that the processes leading to loss of CA1 neurons are modified when the ischemic period is extended. Previous findings that 1,3-butanediol reduced damage in other ischemia-susceptible neuronal subpopulations but not in CA1 neurons most likely reflected the longer period of ischemia which was used. The results of the present investigation demonstrate that administration of 1,3-butanediol offers a novel approach for interfering with post-ischemic loss of CA1 neurons following a brief ischemic period which is effective even when initiated after prolonged recirculation periods.
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PMID:Delayed treatment with 1,3-butanediol reduces loss of CA1 neurons in the hippocampus of rats following brief forebrain ischemia. 785 74


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