Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to determine whether oxygen-derived free radicals play a role in the pathogenesis of gastric lesions produced by hemorrhagic shock in the rat. Allopurinol (Zyloric), an inhibitor of xanthine oxidase (responsible for the formation of superoxide radicals) and MTDQ-DA (Kontrad), a synthetic antioxidant of dihydroquinoline type were used. In the anesthetized rat 0.1 N HCl was instilled into the stomach and the rat was bled to reduce the blood pressure to 30 mmHg for 20 min. The blood shed was retransfused. Twenty min later the stomach was removed. The area of gastric mucosal lesions were measured, the activity of endogenous peroxidase was examined histochemically and a histological grading was made. Both allopurinol and MTDQ-DA significantly protected against hemorrhagic shock-induced gastric lesions and peroxidation. These results suggest that oxygen-derived free radicals play an important role in the formation of gastric lesions produced by ischemia plus 0.1 N HCl.
 ...
PMID:Role of oxygen-derived free radicals in hemorrhagic shock-induced gastric lesions of rats. 259 23

Excessive accumulation of hydrogen ions in the brain may play a pivotal role in initiating the necrosis seen in infarction and following hyperglycemic augmentation of ischemic brain damage. To examine possible mechanisms involved in hydrogen ion-induced necrosis, sequential structural changes in rat brain were examined following intracortical injection of sodium lactate solution (pH 4.5), as compared with injections at pH 7.3. Following pH 7.3 injection, neuronal swelling developed between 1 and 6 h, but only a needle track wound surrounded by a thin rim of necrotic neurons and vacuolated neuropil was present 24 h after injection. In contrast, pH 4.5 injection produced neuronal necrosis as soon as 1 h after injection, followed by necrosis of astrocytes and intravascular thrombi at 3 and 6 h. Alterations common to both groups included vascular permeability to horseradish peroxidase, dilation of extracellular spaces, astrocyte swelling, capillary compression, and vascular stasis. These data suggest that neurons, astrocytes, and endothelia can be directly damaged by increased acid in the interstitial space. Lethal injury initially appeared to affect neurons, while subsequent astrocyte necrosis and vascular occlusion may damage tissue by secondary ischemia.
 ...
PMID:Light and electron microscopic evaluation of hydrogen ion-induced brain necrosis. 282 Oct 31

The hydroxyl radical is one of the most damaging oxygen metabolites that are thought to be produced during ischemia and reperfusion of cardiac tissue. Therefore, we used the isolated, isovolumetric, buffer-perfused rat heart preparation of cardioplegic arrest to assess the effects of interventions targeted at inhibiting production of the hydroxyl radical by decreasing either the availability of one of its precursors (hydrogen peroxide) or that of the metal catalyst (ferric iron) involved in the radical formation. Sixty hearts were studied and, except for nonischemic controls, were subjected to 3 hr of hypothermic (15 degrees to 18 degrees C) cardioplegic arrest, followed by 45 min of reperfusion. The following interventions were tested: pretreatment with peroxidase, a scavenger of hydrogen peroxide, pretreatment with a combination of peroxidase and the iron chelator deferoxamine, pretreatment with peroxidase followed by supplementation of the cardioplegic solution with deferoxamine, and supplementation of the cardioplegic solution with deferoxamine without preischemic enzymatic treatment. Based on comparisons of postreperfusion pressure development, maximal ventricular dP/dt, left ventricular compliance, and coronary flow, deferoxamine-containing cardioplegic solution alone afforded the best myocardial protection. This may be due to the ability of deferoxamine to act both as an iron chelator and as a direct scavenger of superoxide anion, an activated oxygen species that participates in hydroxyl radical formation. This study confirms that an important component of the cardiac damage sustained during global ischemia and reperfusion may involve injury caused by the hydroxyl radical. Furthermore, our results point out the potential therapeutic usefulness of deferoxamine in the context of cardioplegic protection during open-heart procedures.
 ...
PMID:Prevention of hydroxyl radical formation: a critical concept for improving cardioplegia. Protective effects of deferoxamine. 282 88

Some publications have pointed out that oxygen free radicals can induce injury of vessel wall and increase platelet aggregation and clotting, which can suppose a dependent relationship with arteriosclerotic process. We therefore studied the hypothesis of a possible abnormal platelet antioxidant enzymatic equipment in arteriopathic patients. A control group of 20 healthy subjects and an other one of 40 non diabetic patients with peripheral arterial disease were investigated, and the following tests were performed: measure of transcutaneous oxygen tension (PTCO2), determination of activity of platelet superoxide dismutase (SOD), glutathione-peroxidase (G-Px) and catalase (CAT). A significant decrease of SOD and G-Px is observed in platelets of arteriopathic patients. This decrease seems to be correlated with the severity of ischemia. The pathological reduction of platelet antioxidant equipment can be one factor enhancing thrombotic complications in chronic arterial disease.
 ...
PMID:[Platelet antioxidant enzyme activities in arteriopathy]. 282 99

Superimposition of cardioplegic arrest on acute low-cardiac-output states, as may occur after failure of percutaneous transluminal coronary angioplasty requiring emergency surgery, is associated with an increased operative risk. This increased risk is possibly attributable to reperfusion, which, after sequential episodes of myocardial ischemia, exacerbates tissue injury mediated by oxygen free radicals. One of the most cytotoxic of these active oxygen species is the hydroxyl radical, which is formed from superoxide anion and hydrogen peroxide through an iron-catalyzed reaction. This study assesses the effects of peroxidase, a hydrogen-peroxide scavenger, and of deferoxamine, an iron chelator, in isolated working rat hearts subjected to 30 minutes of low-flow ischemia (75% reduction in coronary flow) followed by 2 hours of cardioplegic arrest at 15 degrees C and by 30 minutes of normothermic reperfusion. Three groups of hearts (n = 7) were studied. Two groups were pretreated with either peroxidase (10,000 units/l) or deferoxamine (0.03 mM) during the last 15 minutes of the low-flow ischemic period. The third group received no prearrest intervention and served as a control group. In addition to hemodynamic determination, high-energy phosphate content [adenosine 5'-triphosphate (ATP)] and intracellular pH were monitored serially by 31P nuclear magnetic resonance spectroscopy. The two pretreated groups had better recovery of ATP levels and aortic flow values than did the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cardioplegic arrest superimposed on evolving myocardial ischemia. Improved recovery after inhibition of hydroxyl radical generation by peroxidase or deferoxamine. A 31P nuclear resonance study. 284 3

If myocardial ischemia always results from an imbalance between the needs and supplies in oxygen of the myocardium cells, the physiopathology of this process seems today infinitely more complex than the mere diminution or interruption of the output in a coronary artery. The extension of atheromatous lesions, the platelets aggregation, thrombosis, the coronary spasm, the release of products from the arachidonic cascade, the reactivity of the vascular endothelium, the profibrinolytic activity of the tissues are many of the intricate factors inducing myocardial ischemia. Cellular alterations, of which some are triggered by the release of oxygenated free radicals, lead then to an irreversible necrosis. The medications used until now in the treatment of angina are oxygen scavengers and research goes on in this direction with vaso-dilators beta-blockers, prolonged action nitro-compounds (nicorandil) or nitro-compounds with an action reinforced by N-acetyl-cysteine, bradycardiac derivates of alinidine and the new calcium antagonists dihydropyridine. However, the new physiopathological concepts of ischemia have opened new directions for the research: products which modify the arachidonic cascade by increase of synthesis or release of PGI2 (nafazatrom, defibrotide), by inhibition of TXA2 synthesis or blocking of TXA2 receptors, and similar products of PGI2 (iloprost); thrombolytic agents more specific of thrombin (PTA) or fibrinolysis activators (defibrotide), and anticoagulants with extended action; chelating agents of oxygenated free radicals (peroxide dismutase, catalase, peroxidase) or xanthine oxidase inhibitors; platelets anti-aggregates like ticlopidine which blocks the platelets receptors to fibrinogen, or inhibitors of the synthesis of pro-aggregating agents.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Current therapeutic concepts in the treatment of myocardial ischemia. Current and future drugs]. 287 4

Effects of ischemia on cell membrane of rat heart were investigated. The endothelial surface revealed the existence of ruthenium red-positive glycocalyx at the anionic site. Membrane bound enzyme as Na-K ATPase was mostly located in the inner side and pinocytotic vesicles of endothelial cell. The clumping and dispersion in glycocalyx of endothelial cells was observed in an ischemic heart and it may prove the functional disturbance of plasma membrane. A potential and functional defect with reduced activity of Na-K ATPase occurred within 1 hr of vascular ligation. The membrane dysfunction due to these molecular changes has been proved by the membrane permeability alteration as well as the intracytoplasmic localization of horseradish peroxidase as tracer.
 ...
PMID:Early membrane damage during ischemia in rat heart. 300 26

Oxygen-derived free radicals play an important role in the myocardial injury associated with ischemia and reperfusion. This study was designed to assess whether the protection afforded by a K+ rich, Mg2+ rich cardioplegic solution could be enhanced by the addition of free radical scavengers acting at different levels of the radical generating pathway. Forty isolated isovolumic rat hearts were divided into five groups (n = 8). Four groups of hearts were subjected to 90 minutes of normothermic cardioplegic arrest followed by 45 minutes of reperfusion. Hearts were given an initial bolus of either unmodified cardioplegic solution or cardioplegic solution enriched with superoxide dismutase (200,000 U/L) reduced glutathione (0.1 mmol/L), or peroxidase (6,000 U/L). One group of hearts was aerobically perfused throughout the experimental protocol and served as nonischemic controls. Based on comparisons of postreperfusion ventricular pressure development, maximal ventricular dP/dt, left ventricular compliance and coronary flow, peroxidase-containing cardioplegic solution afforded the best myocardial protection, with values of these indicators not significantly different from those of nonischemic perfused control heart. Glutathione afforded protection slightly inferior to that of peroxidase but still markedly better than in groups receiving superoxide dismutase or unmodified cardioplegic solution. This study confirms that cardioplegic protection can be enhanced by the addition of free radical scavengers, in particular peroxidase.
 ...
PMID:A comparative study of free radical scavengers in cardioplegic solutions. Improved protection with peroxidase. 301 15

This study assesses the ability of the free-radical scavenger peroxidase to enhance cardioplegic protection when given during or before myocardial ischemia. Forty-four isolated isovolumetric buffer-perfused rat hearts were studied. In a first series of experiments that consisted of three groups, hearts were subjected to 90 min of normothermic global ischemia followed by 45 min of reperfusion. One group received a crystalloid cardioplegic solution given as a single dose at the onset of arrest. A second group received cardioplegic solution supplemented with superoxide dismutase (200,000 U/liter), and a third group received cardioplegic solution supplemented with peroxidase (6000 U/liter). Based on comparisons of postreperfusion coronary flow, left ventricular developed pressure, maximum dP/dt, and diastolic pressure, we found that the best protection was provided by peroxidase-enriched cardioplegia. A second series of experiments was then undertaken to assess the effects of the latter enzyme given as a pretreatment. Hearts were subjected to 3 hr of global ischemia, during which myocardial protection was provided by hypothermia (15 degrees C) along with multidose cardioplegia. The treatment group was given peroxidase (10,000 U/liter) added to the perfusate fluid for 15 min before the onset of cardioplegic arrest without further enzyme supplementation during ischemia or reperfusion. Hearts perfused with standard buffer for an equal period of time served as controls. While the two groups demonstrated the same degree of postischemic increase in myocardial stiffness, peroxidase-pretreated hearts had a significantly better recovery of contractile indexes at 30 and 45 min of reflow.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Enhancement of cardioplegic protection with the free-radical scavenger peroxidase. 302 57

There is controversy over the existence of a lateral "border zone" of intermediately injured tissue in the developing myocardial infarct (MI). The authors attempted an ultrastructural demonstration of this zone in serial subepicardial biopsies from developing MIs in dogs subjected to 90 minutes, 6 hours, or 24 hours of left anterior descending coronary artery ligation (4 dogs per group). After ligation, 400,000 units of horseradish peroxidase was infused through the left atrial appendage as a blood flow marker, to allow distinction of perfused and ischemic myocytes under electron microscopy. Evans blue stain was infused in the same way for gross guidance in harvesting biopsies across the lateral margins of the ischemic region. Interdigitation of perfused and ischemic tissue was observed over a lateral margin 6 mm wide, which caused admixture of perfused and ischemic myocytes in biopsies from this region. Ultrastructural ischemic injury was graded on a five-level qualitative scale (normal, mild, moderate, severe, lethal). Perfused myocytes from control and border sites were equivalently well preserved (79% normal, 21% mild injury, n = 353). Ischemic myocyte injury increased with duration of ischemia. At 90 minutes, 65% of ischemic myocytes had mild injury, 35% moderate (n = 138); at 6 hours, 17% of ischemic myocytes had moderate injury, 81% severe, 2% lethal (n = 115); at 24 hr, 100% of ischemic myocytes had lethal injury (n = 148). Severity of ischemic myocyte injury did not vary from the lateral border to the center of the ischemic region: there was no lateral "border zone." However, if myocytes were not separated into perfused and ischemic subpopulations before statistical comparison of biopsy site to severity of injury, false evidence of a "border zone" was obtained.
 ...
PMID:The "border zone" in myocardial infarction. An ultrastructural study in the dog using an electron-dense blood flow marker. 338 78


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>