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)

Kupffer cells and polymorphonuclear leukocytes (PMNs) contribute to the severe reperfusion injury of the liver after ischemia at different time points. The objective of this study was to identify the cellular source(s) of reactive oxygen formation during the PMN-induced injury phase. Kupffer cells and PMNs were isolated from the liver after 45 min of ischemia and 5 h or 24 h of reperfusion using collagenase-pronase digestion and a centrifugal elutriation method. Spontaneous superoxide anion (O2-) formation by large Kupffer cells (basal value 0.65 +/- 0.16 nmol/h/10(6) cells) was increased (up to 550%) during the entire reperfusion period. No enhanced O2- generation by the small Kupffer cell fraction was observed at any time. Control PMNs generated only small amounts of O2- spontaneously (0.25 +/- 0.05 nmol O2-/h/10(6) cells), but hepatic PMNs generated significantly more superoxide: 1.90 +/- 0.58 nmol O2-/h/10(6) cells at 5 h and similarly at 24 h of reperfusion. All cell types were significantly primed for enhanced O2- formation during reperfusion; the priming effect was consistently higher for stimulation with opsonized zymosan (receptor-mediated signal transduction pathway) compared to phorbol myristate acetate (protein kinase C activation). Our data support the hypothesis that PMNs and large Kupffer cells are predominantly responsible for the postischemic oxidant stress during the later reperfusion injury phase after hepatic ischemia in vivo.
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PMID:Superoxide generation by neutrophils and Kupffer cells during in vivo reperfusion after hepatic ischemia in rats. 132 39

We used a cytochemical technique for the detection of superoxide in cerebral inflammation and ischemia-reperfusion in anesthetized cats. The technique is based on the oxidation of Mn2+ to Mn3+ by superoxide; Mn3+, in turn, oxidizes diaminobenzidine. The oxidized diaminobenzidine forms an osmiophilic electron-dense product that is detected by electron microscopy. The reagents, manganese chloride (2 mM) and diaminobenzidine (2 mg/ml), were placed topically on the brain surface of anesthetized cats equipped with cranial windows. Inflammation was induced by topical carrageenan with or without phorbol 12-myristate 13-acetate to activate leukocytes. In inflammation, superoxide was detected in the plasma membrane and in the phagocytic vacuoles of leukocytes. In ischemia-reperfusion, superoxide was identified in the meninges in association with blood vessels. It was located primarily in the extracellular space and occasionally in endothelial and vascular smooth muscle cells. In both inflammation and ischemia, the reaction product was eliminated by superoxide dismutase or by the omission of either manganese or diaminobenzidine. It was unaffected by sodium azide, which inhibits peroxidases. No superoxide was detected in the brain parenchyma. The findings confirm the generation of superoxide is cerebral ischemia-reperfusion and show that it is produced in cerebral vessels.
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PMID:Cytochemical detection of superoxide in cerebral inflammation and ischemia in vivo. 132 63

The role of NO-formation induced by accumulated endogenous bradykinin (BK) via local ACE-inhibition with ramiprilat (RT) or by adding BK exogenously was evaluated in cultured bovine aortic endothelial cells (BAEC) and in isolated rat hearts with post-ischaemic reperfusion injuries. Furthermore we used the n-octyl-ester of ramipril (RA-octil) which was shown to have no ACE-inhibitory action. In BAEC, ACE-inhibition by RT (1 x 10(-8)-1 x 10(-6) mol/l) or addition of BK (1 x 10(-8)-1 x 10(-6) mol/l) stimulated the formation of NO and prostacyclin (PGI2) as assessed by endothelial cyclic GMP- and 6-keto-PGF1a formation. Cyclic GMP and PGI2 synthesis was completely suppressed by the NO synthase inhibitor NG-nitro-L-arginine (L-NNA, 1 x 10(-5) mol/l) and by the B2 kinin receptor antagonist HOE 140 (1 x 10(-7) mol/l). RA-octil (1 x 10(-8)-1 x 10(-4) mol/l) did not affect endothelial cyclic GMP production in BAEC. In isolated working rat hearts subjected to local ischemia with reperfusion both RT (1 x 10(-8) mol/l) and BK (1 x 10(-9) mol/l) reduced the incidence and duration of ventricular fibrillation. In parallel myocardial function (left ventricular pressure, coronary flow) and metabolism (high energy rich phosphates) were improved showing a comparable fingerprint for RT and BK. Addition of L-NNA (1 x 10(-6) mol/l) or HOE 140 (1 x 10(-9) mol/l) abolished these protective effects of RT and BK. As in the BAEC studies RA-octil was without beneficial effects on the isolated ischaemic rat heart. The findings on BAEC show that inhibition of ACE localized on the luminal side of the vascular endothelium results in increased synthesis of NO and prostacyclin by local accumulation of endothelium-derived BK. Similar mechanisms may occur in the ischaemic rat heart leading to cardioprotection.
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PMID:ACE-inhibition induces NO-formation in cultured bovine endothelial cells and protects isolated ischemic rat hearts. 133 74

It has been known for a long time that systemic infusion of angiotensin II in patients with coronary artery disease or normal control subjects causes a marked increase in left ventricular end diastolic pressure (LVEDP) and systolic pressure (LVP) (1,2). In this setting angiotensin II produces a marked increase in afterload that makes it difficult to acknowledge possible local myocardial effects of the peptide. The studies (3-8) summarized in the present paper were designed to examine the physiological role of local cardiac angiotensin II generation and local bradykinin degradation on cardiac function in the normal and hypertrophied rat heart. Angiotensin I and angiotensin II, infused in isolated, well oxygenated, buffer perfused normal rat hearts, produced a mild increase in LVEDP with no change in systolic function (3). In contrast, in hypertrophied rat hearts, angiotensin I and angiotensin II caused a marked deterioration of diastolic function, increasing LVEDP from 10 to 25-37 mmHg on average (3,5). Preliminary evidence suggests that angiotensin II effects on diastolic function are mediated via a protein kinase C dependent pathway that might involve Na+/H+ exchange (4,5). When cardiac angiotensin converting enzyme was blocked by infusion of an ACE inhibitor prior and in parallel to angiotensin I infusion no changes in diastolic function were noted (6). Furthermore, ACE inhibition blunted the diastolic dysfunction during low flow ischemia in isolated hypertrophied rat hearts (7). This effect of ACE inhibition was even more remarkeable, since no exogenous angiotensin was infused in this experiment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiac angiotensin converting enzyme and diastolic function of the heart. 133 46

The effects of ulinastatin (ULN), a human urinary protease inhibitor, on liver injury caused by ischemia-reperfusion were studied in rats. In the liver ischemia-reperfusion model, ULN suppressed the elevation of serum transaminase levels and tissue lipid peroxide levels in the liver. ULN did not exhibit a radical-trapping action on the superoxide and hydroxyl radicals as measured by electron spin resonance (ESR). ULN suppressed formylmethionyl-leucyl-phenylalanine (FMLP) and phorbol myristate acetate (PMA)-induced superoxide production from polymorphonuclear leukocytes (PMNs) as measured by the cytochrome c assay. ULN did not inhibit either xanthine oxidase (XO) activity or the conversion of xanthine dehydrogenase (XDH) to XO during the ischemic period. ULN also strongly protected against the hypotonic hemolysis of rat erythrocytes. These results suggest that ULN's membrane stabilizing action and suppressive effect against PMNs superoxide production might be attributed to its suppressive effect on the liver's lipid peroxidation caused by ischemia-reperfusion.
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PMID:Protective effect of ulinastatin against liver injury caused by ischemia-reperfusion in rats. 133 29

Recent studies suggest that granulocytes (PMNs) play a role in the pathogenesis of acute and chronic myocardial ischemia and extension of myocardial injury. Granulocytes can release a variety of molecules mediating tissue injury which act synergistically with other molecules and cells. The aim of our investigation was to evaluate the granulocyte function in patients affected by coronary artery disease (CAD) and during coronary angioplasty (PTCA). We studied 20 patients suffering from CAD. The PMN's aggregating activity was greater in the coronary sinus than in the aorta (P < 0.01). The increase in aggregating activity was evident in patients who were smokers: their cells release significantly lower quantities of leukotriene C4 (P < 0.025). In the 20 patients who underwent coronary angioplasty we analyzed superoxide release after stimulation with phorbol-myristate-acetate (PMA). The results showed a greater decrease of PMN's superoxide production in the coronary sinus than in the aorta (P < 0.05). In all patients affected by CAD we evaluated the PMN's expression of CD11b/CD18 membrane integrins. In these patients the increase in expression of CD11b/CD18 was statistically significant in comparison with the controls (P < 0.01). This increase in expression correlates with a higher aggregation (r = 0.87, P < 0.001). The potential role of leukocytes, oxygen radicals, leukotrienes and granulocyte enzymes in the pathophysiology of myocardial injury due to regional ischemia and reperfusion is an area of intense investigation. This paper presents studies carried out in vivo which have been instrumental in demonstrating the role of granulocytes as mediators of myocardial ischemia.
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PMID:Phagocyte activation in coronary artery disease. 136 45

The role of neutrophils (PMN) in acute renal failure (ARF) is controversial. Although the development of acute renal failure (ARF) frequently occurs in situations where there is partial activation of PMN (primed PMN) and mild renal ischemia, the interaction between primed PMN and ischemic organs has not been studied in any biological system. To define the interaction between primed PMN and mild renal ischemia, kidneys were made ischemic for 10 minutes in situ and reperfused by the isolated kidney technique with untreated PMN or PMN primed with low concentrations of lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). We found that primed PMN had no effect on control (non-ischemic) kidneys and that untreated PMN did not cause injury to kidneys previously subjected to mild ischemia. However, addition of primed PMN to mildly ischemic kidneys caused severe injury. To determine the nature of renal injury, ischemic kidneys were reperfused with primed PMN and catalase (CAT) or the elastase inhibitor, Eglin C. In ischemic kidneys reperfused with LPS-primed PMN, Eglin C (but not CAT) was partially protective while in ischemic kidneys reperfused with PMA-primed PMN, CAT (but not Eglin C) was partially protective. Reperfusion with both CAT and Eglin C completely prevented the damaging effects of either LPS- or PMA-primed PMN. In conclusion, addition of primed but not untreated PMN causes ARF in mildly ischemic kidneys by PMN oxidant- and/or protease-mediated mechanisms. This synergism could account for the high frequency of ARF in conditions associated with prerenal azotemia and primed PMN.
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PMID:Mild renal ischemia activates primed neutrophils to cause acute renal failure. 140 39

Ischemia-like brain damage was induced in cats by selective injection of 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) into the left carotid artery. PMA-injection provoked significant decreases in platelet and neutrophil counts due to their intravascular aggregation. Platelet and neutrophil aggregates caused brain edema with accumulation of sodium fluorescein in the cerebrospinal fluid and ipsilateral derangement of the cerebral energy state in the parietal cortex. Neurotropin administration decreased the changes in platelet and neutrophil counts and prevented the developments of both brain edema and cerebral energy failure.
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PMID:Cerebrovascular injuries induced by activation of platelets and leukocytes in vivo and their correction by neurotropin. 146 Aug 5

Restoration of coronary blood flow in the ischemic myocardium is absolutely needed to prevent irreversible cellular damage but on the other hand may have potentially hazardous consequences. Since thrombolysis during myocardial infarction is designed to salvage a maximal number of myocardial cells threatened by ischemia, a concommitant intervention which reduces cellular damage due to reperfusion will improve the net result of such procedure. The adjunctive use of ACE-inhibitors with thrombolytic therapy early during acute myocardial infarction offers theoretic advantages. This article summarizes the results indicating that ACE-inhibitors do play an important role in cardioprotection in the acute phase of myocardial ischemia followed by reperfusion. Probably, their effect on bradykinin breakdown is at least partly responsible for this effect.
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PMID:Early ACE-inhibition in myocardial infarction. Possible role of bradykinin. 146 86

In experimental ischemic dog heart with coronary-constriction, no increase of coronary blood flow, Max dP/dt or MVO2 with no change of kinin in arterial blood were exhibited. Following sympathetic nerve stimulation, remarkable increases of kinin in coronary sinus blood were observed with a significant elevation of left ventricular end-diastolic pressure and an augmented production of lactate from the heart as well as an ischemic change of ECG-ST. Infusion of kinin into the left main coronary artery resulted in no change in the mean systemic blood pressure, coronary blood flow, coronary vascular resistance, cardiac function, myocardial metabolism or ECG-ST in the control and coronary-constricted groups. These data suggest that kinin was released significantly from the ischemic heart, however, such a level of kinin has no significant effect on coronary circulation or myocardial metabolism. In ischemia-reperfusion rabbit hearts, no significant influence of the ACE inhibitors, captopril and ramiprilat, were observed. Species differences may be responsible for the beneficial role of ACE inhibitors in the limitation of infarct size in the dog hearts, possessing collateral flow, that are not seen in the rabbit heart with poor collateral flow.
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PMID:Activation of kinins on myocardial ischemia. 146 87


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