Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the formation of oxygen-derived free radicals (or reactive oxygen species; ROS) and the release of endogenous opioid peptides (EOP) have been independently reported to be the major arrhythmogenic factors in ischemic hearts, possible relations between these two factors have seldom been investigated. Thus, we studied whether the ROS and EOP were related in the progression of ischemia-induced arrhythmias. Isolated rat hearts perfused in the Langendorff mode were treated with dynorphin A1-13 (kappa EOP receptor agonist), and/or allopurinol (xanthine oxidase inhibitor), before the onset of ischemia induced by ligating the left coronary arteries. Ischemic period lasted for 30 min, during which cardiac rhythms were recorded. At the end of ischemia, hearts were analyzed for the glutathione and ascorbate levels. Allopurinol (100 nmoles/heart) was effective in reducing the severity of arrhythmia (arrhythmia score: Mean +/- SEM 3.00 +/- 0.80 for allopurinol, 5.75 +/- 0.41 for placebo, p < 0.01), while dynorphin (10 micrograms/heart) potentiated the arrhythmia (6.71 +/- 0.52, p < 0.05 vs. placebo). Coadministration of allopurinol and dynorphin was capable of reducing arrhythmia (5.57 +/- 0.65) when compared with the administration of dynorphin alone (6.71 +/- 0.52, p < 0.05). Tissue oxidative stress was evaluated by the concentrations of glutathione (GSH) and ascorbate. Allopurinol did not significantly elevate tissue GSH concentrations (1.46 +/- 0.05 mumoles/g wet wt) in ischemic hearts, while dynorphin alone significantly decreased the GSH concentrations (0.96 +/- 0.08, p < 0.05) when compared with the placebo (1.32 +/- 0.03). The dynorphin-induced GSH decrease cannot be reversed by coadministration with allopurinol (0.90 +/- 0.104). Allopurinol significantly elevated tissue ascorbate levels (0.16 +/- 0.01) when compared with placebo (0.10 +/- 0.01, p < 0.05). Interestingly, dynorphin alone also elevated the tissue ascorbate concentrations (0.16 +/- 0.02). Coadministration of allopurinol and dynorphin further spiked the ascorbate levels (0.28 +/- 0.05, p < 0.01). In conclusion, the results suggested that ischemia-induced arrhythmia mechanisms might involve the formation of superoxide and other ROS, which were probably generated from the release of EOP (or EOP/EOP receptor interactions). Superoxide, the formation of which can be inhibited by allopurinol that exerted antiarrhythmic effect, was probably scavenged by ascorbate in myocardial ischemia. The ROS resulting from EOP/EOP receptor interactions were probably scavenged by glutathione system. Elevated ascorbate levels in dynorphin-treated hearts might result from the compensatory synthesis induced by decreased glutathione levels.
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PMID:The roles of reactive oxygen species and endogenous opioid peptides in ischemia-induced arrhythmia of isolated rat hearts. 910 Dec 52

Several studies report that among the antioxidant agents used to reduce injury after myocardial ischemia/reperfusion, analogues of vitamin E (VE) seem to have a significant efficacy. Raxofelast is a potent antioxidant agent under investigation, structurally related to VE, having an excellent bioavailability and favourable physicochemical properties. We assessed raxofelast in a rat model of myocardial damage induced by 1 h of left coronary artery occlusion followed by 6 h of reperfusion. Myocardial ischemia/reperfusion produced: wide tissue necrosis (50.3+/-10.3%); membrane peroxidation, evaluated by assessing cardiac malondialdehyde (MAL) (87.8+/-15.8 nmol/g tissuev 9.53+/-2.4 nmol/g tissue) and plasma conjugated dienes (CD) (8.73+/-1.86 DeltaABS/mlv 1.61+/-0.45 DeltaABS/ml); endogenous antioxidant wasting [cardiac VE=23.5+/-10.2 nmol/g tissuev 61.4+/-13.4 nmol/g tissue, cardiac reduced glutatione (GSH)=2.15+/-1.23 micromol/g proteinv 7.34+/-0.92 micromol/g protein and cardiac superoxide dismutase (SOD)=8.9+/-4.1 U/mg proteinv 17. 5+/-4.2 U/mg protein]; depressed mean arterial blood pressure (MAP) (61.4+/-5.8 mmHgv 85.3+/-6.2 mmHg); heart rate (HR) (275+/-35 beats/minv 368+/-34 beats/min) and left-ventricular derivative developed force (LV dP/dtmax) (1050+/-187 mmHg/sv 2520+/-194 mmHg/s); and cardiac neutrophil accumulation, evaluated by assessing cardiac myeloperoxidase (MPO) (9.23+/-2.1 U/g tissuev 0.92+/-0.12 U/g tissue). Administration of raxofelast (25, 50 and 100 mg/kg i.p. 5 min after occlusion) limited myocardial necrosis (22.3+/-14.8%P<0. 005, following the highest dose), reduced lipid peroxidation (MAL=43. 5+/-14.7 nmol/g tissueP<0.001 and CD=4.01+/-2.21 DeltaABS/mlP<0.001, following the highest dose), restored the endogenous antioxidants VE (52.8+/-14.2 nmol/g tissueP<0.001, following the highest dose), SOD (14.2+/-2.7 U/mg proteinP<0.001, following the highest dose) and GSH (4.92+/-1.33 micromol/g proteinP<0.005, following the highest dose), improved hemodynamic parameters (MAP=68.1+/-5.3 mmHgP<0.05, HR=317+/-27 beats/minP<0.05, LV dP/dtmax=1427+/-143 mmHg/sP<0.05, following the highest dose) and reduced myocardial neutrophil infiltration (MPO=5.1+/-1.5 U/g tissueP<0.001, following the highest dose). These data suggest that raxofelast could be considered a useful drug to reduce myocardial infarction.
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PMID:Beneficial effect of raxofelast, an hydrophilic vitamin E analogue, in the rat heart after ischemia and reperfusion injury. 973 36

An ethyl acetate extract of Polygonum multiflorum Thunb. (PME) was fractionated into an anthraquinone-containing (PME-I) and a non-anthraquinone-containing (PME-II) fraction. The effects of PME and its related extracts pretreatment on myocardial ischemia-reperfusion (IR) injury in isolated perfused rat hearts were examined. Pretreatment with PME extract or its anthraquinone-containing fraction produced a dose-dependent protection against myocardial IR injury, as evidenced by a significant decrease in the extent of LDH leakage as well as an improvement in contractile force recovery. The myocardial protection was found to be associated with an enhancement in myocardial glutathione antioxidant status, as indicated by significant reductions in both the extent of IR-induced reduced glutathione (GSH) depletion and inhibition of Se-glutathione peroxidase (GPX) and glutathione reductase (GRD) activities. Both alpha-tocopherol acetate (VE) and emodin (EMD) pretreatments protected against IR-induced myocardial injury as assessed by the decrease in the extent of LDH leakage. But the contractile force recovery of the ischemic-reperfused hearts prepared from VE or EMD pretreated animals was not improved. The more complete myocardial protection afforded by the anthraquinone-containing fraction of PME extract may be related to its ability to sustain the glutathione antioxidant status under the condition of IR-induced oxidative stress.
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PMID:Myocardial protective effect of an anthraquinone-containing extract of Polygonum multiflorum ex vivo. 981 Feb 65

Myocardial ischemia and reperfusion result in endothelial and ventricular dysfunction. Beta-blockers protect the myocytes from injury by acting as anti-ischemia agents. These anti-ischemic effects of the beta-blockers are due not only to their negative inotropic/chronotropic effects but also to a lipid peroxidation reducing mechanism. Thus, beta-blockers enhance myocardial recovery. In the present study 20 isolated guinea-pig hearts were perfused with Krebs-Henseleit buffer (KHB) using a Langendorff apparatus. The animals were allocated into 2 groups. In the study group (Group I), metoprolol, as the beta-blocker agent, was added into the KHB and in the control group (Group II) perfusion was performed without metoprolol. The percentage change (%change) of heart rate, developed pressure and dP/dtmax; malondialdehyde (MDA) and glutathione (GSH) levels of the perfusate and heart tissue were obtained as data. The %change of heart rate was 70.5+/-9.2 in the study group and 87.3+/-8.2 in the control (p = 0.003). The %change of developed pressure was 68.7+/-14.4 and 55.9+/-8.6 in the study group and control group, respectively (p = 0.04). The % change of dP/dt was 63.3+/-10.0 in the study group and 54.4+/-5.3 in the control group (p = 0.01). The tissue MDA level was 31.0+/-5.5 nmol/g tissue in the study group and 53.5+/-4.2 nmol/g tissue in the control group (p = 0.0002). The tissue GSH levels were 1.08+/-0.20 and 0.80+/-0.07 (mol/g tissue) in Groups I and II, respectively (p = 0.001). The levels of the perfusate MDA decreased and the levels of the perfusate GSH increased significantly in the metoprolol group in the postreperfusion period in comparison with the preischemia term (p = 0.003 and p = 0.03, respectively). Metoprolol reduces ischemic injury via prevention of lipid peroxidation and reduces the myocardial energy demand by decreasing the heart rate.
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PMID:Metoprolol prevents ischemia-reperfusion injury by reducing lipid peroxidation. 1049 88

Hypercholesterolemia is a primary risk factor for atherosclerosis, coronary artery disease, and myocardial infarction. We subjected low density lipoprotein receptor-deficient (LDLr -/-) and control (wild-type) mice to 30 minutes of myocardial ischemia and 120 minutes of reperfusion. Myocardial infarction per area at risk (AAR) was noted under baseline conditions to be significantly (P<0.05) smaller in the LDLr -/- mice compared with wild-type mice (24.7+/-3. 2% and 38.8+/-4.3% of AAR, respectively). Subsequently, mice were fed a high-cholesterol diet (HCD) for 2 or 12 weeks, which resulted in significant increases in serum cholesterol levels in both LDLr -/- and wild-type groups. After 2 weeks of the HCD, the LDLr -/- mice demonstrated a significant elevation (P<0.01) in myocardial necrosis per AAR (50.2+/-5.36% of AAR) compared with the normal-diet LDLr -/- group, whereas the short-term HCD-fed wild-type mice demonstrated no significant difference from baseline. In contrast, wild-type mice fed the HCD for 12 weeks revealed a significant (P<0. 05) decrease in necrosis per AAR, which was 22.5+/-3.2% of the AAR in comparison with that in the normal-diet wild-type mice (38.8+/-4. 3% of AAR). LDLr -/- mice on the same long-term HCD showed a similar significantly (P<0.05) decreased infarct size, which was 13.2+/-4.0% of the AAR. In additional experiments, we determined that myocardial tissue total glutathione (GSH) levels were reduced after 2 weeks of the HCD and were significantly increased after 12 weeks of the HCD in the LDLr -/- mouse heart. These data suggest that short-term cholesterol feeding renders the myocardium of LDLr -/- mice more susceptible to ischemia-reperfusion injury, whereas more long-term hypercholesterolemia confers cardioprotection in the LDLr -/- mouse heart.
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PMID:Effects of hypercholesterolemia on myocardial ischemia-reperfusion injury in LDL receptor-deficient mice. 1055 25

Neutrophils may contribute to myocardial ischemia/reperfusion (I/R) injury by generating reactive oxygen intermediates (ROIs). ROIs activate nuclear factor (NF)-kappaB, which regulates genes for cytokines with negative inotropic effects (interleukin [IL]-1beta, IL-6, and tumor necrosis factor [TNF]-alpha). We investigated the impact of neutrophil depletion on NF-kappaB DNA binding activity, and expression of these cytokines during myocardial I/R injury. Male WKY rats (n = 28) received a single dose of antineutrophil antiserum (i/v). Twenty two hours later, when the peripheral blood neutrophil counts were profoundly decreased (94% reduction), the animals underwent 15 min of left anterior descending coronary artery ligation followed by reperfusion for 0.25, 0.5, 1, 2, 3, and 6 h (n = 4/group). Saline-treated animals underwent a similar protocol, and served as controls (n = 28, 4/group). Neutrophil accumulation, defined by myeloperoxidase activity, was present in controls, but not in anti-PMN antisera-treated animals (at least p <0.05 at 1, 2, 3, and 6 h R). Despite this difference, in both saline- and antiserum-treated animals, the GSH levels were very similar and fell significantly (p < 0.0001) at 15 min R; the levels increased gradually over time. In contrast, GSSG levels rose at 15 and 30 min R (p < 0.05), and declined thereafter. NF-kappaB DNA binding activity increased in both groups at 15 min and again at 3 h of R. Both NF-kappaBp50 and p65 subunits were detected by supershift assay. In saline-injected controls both mRNA and protein for IL-1beta, IL-6, and TNF-alpha were detected at 1 h R; levels remained high until 3 h, then fell (except IL-6, which was elevated at 6 h). In neutropenic animals, however, a significant decrease in mRNA (at least 1.7-fold, p < 0.05) as well as protein levels (at least 2. 3-fold, p < 0.01) for all three cytokines was observed. Thus, while neutrophils had minimal effects on oxidative stress (GSH/GSSG) and oxidative stress-responsive NF-kappaB activity, they contributed significantly to myocardial cytokine expression.
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PMID:Induction of nuclear factor kappaB but not kappaB-responsive cytokine expression during myocardial reperfusion injury after neutropenia. 1093 53

The most important risk factors contributing to the development of atherosclerosis include lipid disorders and the predisposition to early ischaemic heart disease in the family. Atherosclerotic process proceeds with age and it develops as a result of oxide LDL modification at the level of vascular wall. Oxygen-free radicals take part in this process, which may probably be opposed by the antioxidant system of the body. The aim of this study was to compare the intensity of lipid peroxidation and the activity of antioxidant enzymes in children from the families with the risk of early atherosclerosis and in children without such predisposition. The activity of katalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined and the concentration of malonic dialdehyde--a lipid peroxidation marker was established. The study was conducted on 76 children aged 4-17 years, mean age 12 +/- 0.6 years. The risk group consisted of 56 patients with the history of hypercholesterolaemia and early atherosclerosis in the members of their families up to 45 years of age. Control group was formed of 20 subjects without such history. MDA concentration as well as the activity of antioxidant enzymes were determined with the use of adequate methods of spectrophotometry. The results obtained were subject to statistical analysis. The activity of antioxidant enzymes displayed considerable fluctuations in both groups of children, but these differences remained statistically insignificant in all the cases. Higher MDA concentrations in serum and in erythrocytes were observed in the risk group. These differences proved statistically significant (alpha < 0.05). On the basis of the present study and the analysis performed, it was found that the activity of antioxidant enzymes (CAT, SOD, GSH-Px) cannot serve as a parameter differentiating between children from the families with the risk of early atherosclerosis and children without such predisposition. Children with positive family history of hypercholesterolaemia and early atherosclerosis may demonstrate intensive lipid peroxidation, but this hypothesis requires further investigations.
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PMID:Enzymatic efficiency of erythrocyte antioxidant barrier and lipid peroxidation in children from families with high risk of early atherosclerosis. 1120 96

We speculate that the glutathione (GSH) status of human subjects could be an indicator of health and functional age. In this regard, in a study in which, 80 young and 40 elderly healthy individuals were selected as control. We also studied 145 patients with chronic illnesses namely, ischaemic heart disease, diabetes, preeclampsia, cataract, chronic renal failure and leukaemia (age 52 +/- 8.6 years). We observed that all the subjects had high malonadildehyde and low glutathione levels as compared to control. These early observations support the hypothesis that oxidative stress may have an important aetiological rule and antioxidants a potential therapeutic role.
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PMID:Glutathione levels in health and sickness. 1127 24

Extensive evidence suggests that reactive oxygen species are critically involved in the pathogenesis of cardiovascular diseases, such as atherosclerosis and myocardial ischemia-reperfusion injury. Consistent with this concept, administration of exogenous antioxidants has been shown to be protective against oxidative cardiovascular injury. However, whether induction of endogenous antioxidants by chemical inducers in vasculature also affords protection against oxidative vascular cell injury has not been extensively investigated. In this study, using rat aortic smooth muscle A10 cells as an in vitro system, we have studied the induction of cellular antioxidants by the unique chemoprotector, 3H-1,2-dithiole-3-thione [corrected] (D3T) and the protective effects of the D3T-induced cellular antioxidants against oxidative cell injury. Incubation of A10 cells with micromolar concentrations of D3T for 24 h resulted in a significant induction of a battery of cellular antioxidants in a concentration-dependent manner. These included reduced glutathione (GSH), GSH peroxidase, GSSG reductase, GSH S-transferase, superoxide dismutase, and catalase. To further examine the protective effects of the induced endogenous antioxidants against oxidative cell injury, A10 cells were pretreated with D3T and then exposed to either xanthine oxidase (XO)/xanthine, 4-hydroxynonenal, or cadmium. We observed that D3T pretreatment of A10 cells led to significant protection against the cytotoxicity induced by XO/xanthine, 4-hydroxynonenal or cadmium, as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium reduction assay. Taken together, this study demonstrates for the first time that a number of endogenous antioxidants in vascular smooth muscle cells can be induced by exposure to D3T, and that this chemical induction of cellular antioxidants is accompanied by markedly increased resistance to oxidative vascular cell injury.
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PMID:Chemical induction of cellular antioxidants affords marked protection against oxidative injury in vascular smooth muscle cells. 1189 Jun 70

Effects of amino acid composition MP-33 in combination with trimetazidine were studied in metabolic therapy of elderly patients (age 63.3 +/- 1.7 years) with ischemic heart disease (angina pectoris functional class II-III). MP-33 (100 mg 3 times a day subling.), trimetazidine (20 mg 3 times a day per os), trimetazidine + amino acid composition MP-33 in the above doses in addition to basic therapy were given to 30, 15 and 15 patients, respectively. Combined therapy with trimetazidine and MP-33 significantly activated antioxidant enzymes and depressed lipid peroxidation due to GSH-dependent regulation of cellular redox status by MP-33.
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PMID:[Enhancement of antioxidant status of the elderly patients with ischemic heart disease in response to amino acid composition of MP-33 in combined therapy with trimetazidine]. 1208 89


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