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)

Aspirin is only modestly effective in the secondary prevention after cerebral ischemia. Studies in other vascular disorders suggest that anticoagulant drugs in patients with cerebral ischemia of presumed arterial (noncardiac) origin might be more effective. The aim of the Stroke Prevention in Reversible Ischemia Trial (SPIRIT) therefore was to compare the efficacy and safety of 30 mg aspirin daily and oral anticoagulation (international normalized ratio [INR] 3.0-4.5). Patients referred to a neurologist in one of 58 collaborating centers because of a transient ischemic attack or minor ischemic stroke (Rankin grade < or =3) were eligible. Randomization was concealed, treatment assignment was open, and assessment of outcome events was masked. The primary measure of outcome was the composite event "death from all vascular causes, nonfatal stroke, nonfatal myocardial infarction, or nonfatal major bleeding complication." The trial was stopped at the first interim analysis. A total of 1,316 patients participated; their mean follow-up was 14 months. There was an excess of the primary outcome event in the anticoagulated group (81 of 651) versus 36 of 665 in the aspirin group (hazard ratio, 2.3; 95% confidence interval [CI], 1.6-3.5). This excess could be attributed to 53 major bleeding complications (27 intracranial; 17 fatal) during anticoagulant therapy versus 6 on aspirin (3 intracranial; 1 fatal). The bleeding incidence increased by a factor of 1.43 (95% CI, 0.96-2.13) for each 0.5 unit increase of the achieved INR. Anticoagulant therapy with an INR range of 3.0 to 4.5 in patients after cerebral ischemia of presumed arterial origin is not safe. The efficacy of a lower intensity anticoagulation regimen remains to be determined.
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PMID:A randomized trial of anticoagulants versus aspirin after cerebral ischemia of presumed arterial origin. The Stroke Prevention in Reversible Ischemia Trial (SPIRIT) Study Group. 940 77

Acetylsalicylic acid often is used in the treatment and prophylaxis of regional myocardial ischemia and infarction. However, only little is known about its electrophysiological effects and on possible proarrhythmic effects of the drug. Thus, the aim of this study was to evaluate the electrophysiological effects of acetylsalicylic acid in normal isolated saline perfused rabbit hearts and in hearts submitted to regional ischemia. Isolated saline perfused rabbit hearts were treated with increasing concentrations of acetylsalicylic acid (0.05, 0.1, 0.5 and 1 microM). The epicardial activation and repolarisation process were analysed using an epicardial mapping (256 unipolar leads). Activation and repolarisation time were determined for each electrode from which data the 'breakthrough-points' of epicardial activation were determined. At each electrode an activation vector was calculated giving the direction and velocity of the local excitation wave. The similarity of selected heart beats compared to the control was evaluated by determination of the percentage of identical breakthrough-points and of similar vectors (deviation < or = 5 degrees). At each electrode the local epicardial action potential duration was assessed as the activation recovery interval and the standard deviation of the epicardial action potential duration (of 256 leads, = dispersion) was determined. In a second series of experiments 30 min regional ischemia was induced by occlusion of the left descendent coronary artery followed by 30 min reperfusion in the absence or presence of 0.5 microM acetylsalicylic acid or 1 micro/M indomethacin. The degree of ischemia was assessed by the reduction in coronary flow, by the degree of ST-elevation and by the area in which ST-elevation was registered. Under non-ischemic conditions acetylsalicylic acid led to an increase in the epicardial action potential duration (7%), a decrease in the breakthrough-point similarity (by 10%) and vectorfield similarity (by 15%). In control hearts submitted to regional ischemia the similarity of the vectorfields and of the breakthrough-points, as well as the duration of the epicardial action potentials were markedly reduced while the dispersion was greatly increased. In the ischemic region there was a significant ST-deviation from the isoelectrical line. These changes of ST-segments were significantly enhanced by 0.5 microM acetylsalicylic acid, so that in all (7/7) acetylsalicylic acid treated hearts sustained ventricular fibrillation occurred after 20 min ischemia, whereas in the absence of acetylsalicylic acid fibrillation was found in only 2/7 hearts during reperfusion and not during ischemia. 1 microM indomethacin did not cause these changes. In all ischemia/reperfusion series of experiments the reduction in coronary flow and left ventricular pressure by ischemia was of the same degree and we did not observe significant differences in the size of ischemic area. Using 14C-acetylsalicylic acid, an accumulation of acetylsalicylic acid in the ischemic region could be observed. From these results we conclude, that acetylsalicylic acid can induce ventricular fibrillation. Thus, in acute myocardial ischemia, acetylsalicylic acid may have (besides the well known and desired antiaggregatory effects) electrophysiologic side effects which seem to be proarrhythmic in regional ischemia at least in this model.
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PMID:Acetylsalicylic acid enhances arrhythmogeneity in a model of local ischemia of isolated rabbit hearts. 947 26

Despite diagnostic and therapeutic advances, mesenteric vascular occlusion with intestinal infarction is often fatal. Parameters determining the high mortality are seldom discussed in the literature. By univariate statistical analysis we correlated the therapeutic outcome of our patients to 20 parameters. Between 1 January 1984 and 30 April 1996 we treated 22 men and 18 women with acute bowel ischemia of vascular origin. All patients underwent laparotomy, 40% (n = 16) due to the diagnosis of mesenteric infarction. In 15% (n = 6) the laparotomy was only exploratory; in 34 cases (85%) bowel resection was carried out. Mortality for all patients was 55% (n = 22). Univariate analysis of the 20 parameters showed that the therapeutic outcome was significantly correlated to a pre-existing diabetes, the course of hospitalization, and the high ASA class. There was no correlation to the length of resected bowel. Most parameters that determine the mortality of bowel infarction are pre-existing and cannot be influenced, but survival can be achieved in some patients if radical and aggressive resection is carried out at the side of almost complete small bowel infarction and followed by an elective second-look operation. Even short-bowel syndrome can be treated. Patients can return to a near normal lifestyle with an acceptable quality of life with the aid of parenteral nutrition at home.
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PMID:[Fatal outcome factors of intestinal infarct of primary vascular origin]. 949 3

Since the publication of prior reviews on this topic, substantial clinical experience with a variety of operative strategies to prevent ischaemic cord complications has been reported. The available data on angiographic localisation of critical intercostal vessels, and, in particular, the evoked potential response to cross-clamping in patients indicates that risk of paraplegia varies considerably even among patients with equivalent TAA extent. Factors such as individual development of the ASA, patent critical intercostals, and the particulars of collateral circulation when intercostal aortic ostia are already occluded likely account for this variability. Information available from SSEP monitoring relative to the dynamic course of cord ischaemia with cross-clamping, and the parallel, if not, frustrating experience with angiographic localisation and intercostal vessel reconstruction indicates that a narrow temporal threshold of cord ischaemia with clamping is present in many patients. This reinforces the importance of both expeditious clamp intervals, critical intercostal re-anastomoses, and the desirability of neuroprotective manoeuvres during cross-clamp induced cord ischemia. As suggested in compelling experimental work our contemporary clinical experience, and predicted by prior reviewers, regional cord hypothermia provides significant promise for limiting or eliminating, in particular, immediate perioperative deficits. Avoidance of postoperative hypotension, spinal cord oedema, and preservation of critical intercostal vessels are additional strategies necessary to impact the development of delayed deficits favourably.
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PMID:Prevention of spinal cord ischaemic complications after thoracoabdominal aortic surgery. 955 Oct 47

In recent years, relevant changes have occurred in the knowledge of the cellular mechanisms regulating platelet aggregation and adhesion to the endothelial surface. In particular, major aspects of the interactions between platelets and endothelial cells and neutrophils have been clarified. These interactions involve not only thrombosis-promoting or thrombosis-inhibiting properties but also several aspects of the regulation of vascular function. A new concept has progressively emerged showing thrombosis as a multicellular event in which cell-to cell interactions between platelets, neutrophils, and endothelium regulate the size of a growing thrombus. In brief, there is consistent evidence showing that two vasodilating mediators produced by endothelial cells and neutrophils (nitric oxide and prostacyclin) have antiaggregating platelet effects. Platelet activation is particularly relevant in myocardial ischemia, and several pharmacological strategies have been devised to prevent intravascular platelet activation. Aspirin remains a keystone of these preventive and damage-limiting strategies. Current knowledge maintains that low doses of aspirin decrease in vivo platelet aggregation by a selective inhibitory effect on thromboxane A2 production by platelets with maintenance of prostacyclin production by the endothelium. We have recently focussed our research on the basis that the antiaggregating effect of aspirin could be explained not only by the above-mentioned effects on thromboxane A2 synthesis, but also through its action on neutrophils. Our in vitro and ex vivo studies have demonstrated that neutrophils enhance the antiaggregating effects of acetylsalicilic acid on platelets. We have shown that acetylsalicilic acid stimulates nitric oxide production on neutrophils inhibiting the aggregating effects of thrombin, ADP or epinephrine on platelets. the role of the neutrophils in ischemic events enhancing the tissue damage through the release of several proteases, reactive oxygen species and tumor necrosis factor-alpha has been extensively demonstrated. In an experimental model of acute ischemia/reperfusion in rabbits, we have shown that acetylsalicilic acid is able to enhance the nitric oxide production by neutrophils providing a potential mechanism for the beneficial action of aspirin in the myocardial infarction. Further research is needed to assess the mechanisms of the action of aspirin during the thrombotic phenomena and its effects on the different types of cells that compound the microvascular environment.
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PMID:[Thrombosis and coronary disease: neutrophils, nitric oxide and aspirin]. 957 62

Polymorphonuclear neutrophils (PMN) and monocytes play a role in vascular diseases. Animal experimental models, using deleukocytation or injection of anti-CD11b-anti-CD18 monoclonal antibodies (inhibition of leukocytic adhesion and of interaction with the endothelial cell) have confirmed this role in the ischemia-reperfusion syndrome and in myocardial infarction. In man, increased production of oxygen radicals, PMN release of elastase, increased monocyte formation of tissue factor (TF) and integrins have been noted in coronary artery disease, in chronic arteriopathy of the lower limbs and in association with vascular risk factors such as diabetes. Pharmacological alteration of leukocyte hyperactivity therefore seems to be justified. Pentoxifylline, used with good effect in arteriopathy of the lower limbs, affects numerous leukocytic functions: diminution in adherence and in PMN production of free radicals, diminution in the formation of TF and cytokines (TNF). Gingkolides reduce leukocytic interactions and platelet activation through an anti-PAF (Platelet Activation Factor) action. Aspirin may interfere with free radicals and inhibit TF formation. alpha-tocopherol blocks the activation, by free radicals, of the transcription factor NF k B. By altering the TNF and IL-1 cytokines, leukocytic activation can be controlled. Other cytokines (IL-4, IL-10) have an immunosuppressive action and reduce the formation of TF. The pharmacological targets are therefore multiple. Their use in vascular diseases is only at a very preliminary stage.
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PMID:[Modulators of leukocytic functions]. 960 25

Aspirin is widely used as an analgesic, in the secondary prevention of stroke, and has recently been suggested to be a putative neuroprotective agent, yet whether it acts directly on the central nervous system (CNS) is not yet clarified. We therefore examined the effect of lysine acetylsalicylate (L-ASA, 4-2000 microM) on neuronal function under normal conditions and following 1 h of ischemia using the in vitro rabbit retina preparation. L-ASA inhibited the light-evoked compound action potentials, but not the electroretinogram, in a concentration-dependent manner. In addition, L-ASA (2000 microM, but not 4, 40 or 200 microM) administered during ischemia, reduced the recovery of neuronal function compared to control (untreated) retinas. L-ASA therefore inhibits CNS neurotransmission, but not phototransduction, in a concentration-dependent manner. In addition, high concentration L-ASA impairs the recovery of neuronal function following an ischemic episode.
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PMID:Acetylsalicylate administered during simulated ischemia reduces the recovery of neuronal function in the in vitro rabbit retina. 968 41

The production of prostacyclin (PGI2) and thromboxane A2 (TXA2) in infarcted and noninfarcted portions of the rabbit heart was studied prior to and following administration of acetylsalicylic acid (aspirin). Aspirin was administered intravenously (iv) as water-soluble Aspisol, d-lysinmono (acetylsalicylate) (Bayer, Leverkusen, Germany) into an ear vein. A branch of the left circumflex coronary artery was ligated. The animals were divided into three groups. The first group received 150 mg/kg/day of aspirin (75 mg/kg of aspirin every 12 h, n = 10). The first administration of aspirin was 1 h after ligation of the coronary artery and the last injection was 1 h before euthanasia. The second group received 5 mg/kg/day of aspirin (every 24 h, n = 10). A separate group of rabbits not receiving aspirin served as controls (n = 12). Two days following onset of ischemia, inducible form of nitric oxide synthase (iNOS) was measured in heart muscle and the oxidation products of nitric oxide (nitrite, NO-2 plus nitrate, NO-3: their sum referred to as NOx) were determined in arterial and coronary venous blood. Concentrations of both PGI2 and TXA2 were elevated in the infarcted portions of the heart compared to the noninfarcted regions. Formation of prostanoids was accompanied by increased activation of iNOS. Both doses of aspirin diminished the concentrations of PGI2 and TXA2 in infarcted heart muscle; in contrast, small doses of aspirin failed to influence myocardial iNOS activity. Apparently small doses of aspirin changed the relationship of iNOS to cyclooxygenase (COX). Coronary arterial-venous difference of NOx and myocardial iNOS activity showed parallel increases. Diminution of prostacyclin by aspirin can damage gastric mucosa and interfere with vasodilatation. Since NO counters these deficiencies, a combination of aspirin with a nitric oxide donor may be advantageous.
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PMID:Production of prostanoids and nitric oxide by infarcted heart in situ and the effect of aspirin. 1019 39

To determine whether ischemia followed by subsequent reperfusion can induce fetal cerebral oxidative damage, we created a model of fetal ischemia/reperfusion using rats at day 19 of pregnancy. Fetal ischemia was induced by unilateral occlusion of the utero-ovarian artery for 20 min. Reperfusion was achieved by releasing the occlusion and restoring the circulation for 30 min. The opposite uterine horn was used as control. We measured brain mitochondrial respiratory control index (RCI) and the concentration of thiobarbituric acid-reactive substances (TBARS) in each group. Arachidonic acid (AA) peroxidation induced by the incubation of brain microvessel fraction and AA was measured. AA peroxidation was also evaluated with and without aspirin, an inhibitor of cyclooxygenase and phenidone, which inhibits both of cyclooxygenase and lipoxygenase. The RCI significantly decreased by the occlusion with (p < 0.01) or without reperfusion (p < 0.05). The TBARS level significantly increased with occlusion plus reperfusion (p < 0.01). AA peroxidation was significantly greater in the occlusion and occlusion plus reperfusion groups than in the control groups (p < 0. 01). Aspirin did not affect peroxidation, while phenidone significantly inhibited it in a concentration-dependent manner (p < 0.001). Accordingly, ischemia followed by reperfusion is likely to induce fetal cerebral lipid peroxidation, which may inhibit mitochondrial respiratory activity. The phenidone-inhibited enzyme lipoxygenase may participate importantly in this peroxidation.
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PMID:Oxidative damage in fetal rat brain induced by ischemia and subsequent reperfusion. Relation to arachidonic acid peroxidation. 1039 92

Many clinical reports have described postoperative hoarseness and sore throat after general anesthesia. In most cases, these symptoms were attributed to high pressure of the endotracheal tube cuff. The recommended cuff pressure is less than 25 mmHg, as excessive pressure produces ischemia of the tracheal mucosa. However, within the safe pressure range, postoperative hoarseness and sore throat are still often observed. In this study, one hundred and ninety patients of ASA classes I or II were allocated randomly to two groups, low cuff pressure group (< 15 mmHg) or high cuff pressure group (15-25 mmHg), using continuous monitoring with a cuff pressure gauge. We investigated the incidence of postoperative hoarseness and sore throat at 24 hours after intubation and on the seventh postoperative day. The incidence of postoperative hoarseness and sore throat was significantly decreased in the low pressure group at 24 hours after intubation as compared with the high pressure group, but there was no significant difference between the two groups on the seventh postoperative day. These results suggest that keeping the cuff pressure under 15 mmHg can prevent postoperative hoarseness or sore throat at 24 hours after intubation, and that a cuff pressure gauge is thought to be one of the indispensable monitors during anesthesia.
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PMID:[Postoperative hoarseness and sore throat after tracheal intubation: effect of a low intracuff pressure of endotracheal tube and the usefulness of cuff pressure indicator]. 1055


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