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)

An elevated peripheral leucocyte count is associated with an increased risk of myocardial infarction and progression of coronary artery disease. The aim of this study was to determine neutrophil count and activation, measured as an increase in plasma neutrophil elastase, in patients with stable ischaemic heart disease, insulin-dependent diabetes mellitus and essential hypertension compared with a comparable group of control subjects. Neutrophil count and neutrophil elastase were raised significantly for patients with ischaemic heart disease (p less than 0.005; p less than 0.002), diabetes mellitus (p less than 0.001; p less than 0.01) and hypertension (p less than 0.05; p less than 0.0001) respectively compared to the control subjects. Neutrophil elastase did not correlate with subject age or leucocyte count. This study confirms the association between leucocyte count and vascular disease, and is consistent with neutrophil activation contributing to the progression of vascular disease.
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PMID:Neutrophil count and activation in vascular disease. 160 64

Activated neutrophils releasing proteolytic enzymes and oxygen free radicals have been implicated in extending myocardial injury after myocardial infarction. Neutrophil elastase was used as a marker of neutrophil activation and the non-peroxide diene conjugate of linoleic acid was used as an indicator of free radical activity in 32 patients after acute myocardial infarction; 17 were treated by intravenous thrombolysis. Patients with acute myocardial infarction had higher plasma concentrations of neutrophil elastase and the non-peroxide diene conjugated isomer of linoleic acid than normal volunteers or patients with stable ischaemic heart disease. Patients treated by thrombolysis had an early peak of neutrophil elastase at eight hours while those who had not been treated by thrombolysis showed a later peak 40 hours after infarction. The plasma concentration of non-peroxide conjugated diene of linoleic acid was highest 16 hours after the infarction irrespective of treatment by thrombolysis. Quantitative imaging with single photon emission tomography showed decreased uptake of indium-111 labelled neutrophils in the infarcted myocardium (as judged from technetium-99m pyrophosphate) in those who had received thrombolysis, suggesting a decreased inflammatory response. The results indicate increased neutrophil activation and free radical production after myocardial infarction; they also suggest that thrombolysis does not amplify the inflammatory response and may indeed suppress it.
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PMID:Inflammatory response, neutrophil activation, and free radical production after acute myocardial infarction: effect of thrombolytic treatment. 231 13

Neutrophils, a source of proteolytic enzymes and oxygen free radicals, have been shown to participate in animal models of myocardial ischemic injury. To characterize neutrophil activation in human ischemic heart disease, a specific neutrophil elastase-derived fibrinopeptide in plasma was measured in 25 patients with stable angina pectoris, 29 patients with unstable angina pectoris, 17 patients with acute myocardial infarction and 22 control subjects. Mean plasma levels (+/- standard error) of a neutrophil elastase-derived fibrinopeptide (B beta 30-43) measured by a specific radioimmunoassay were fivefold higher in patients with acute myocardial infarction (877 +/- 337 pmol/liter, p less than 0.02) and 13-fold higher in patients with unstable angina (2,277 +/- 613 pmol/liter, p less than 0.006) as compared with control subjects (172 +/- 74 pmol/liter). Mean plasma levels of peptide B beta 30-43 in patients with stable angina (676 +/- 334 pmol/liter), although higher than in control subjects, were not significantly increased (p = 0.64). Total leukocyte counts were 11.0 +/- 0.6 x 10(6)/ml in those with acute myocardial infarction, 9.2 +/- 0.7 x 10(6)/ml in those with unstable angina, 7.1 +/- 0.3 x 10(6)/ml in those with stable angina and 7.7 +/- 0.4 x 10(6)/ml in control subjects. Although total leukocyte counts in patients with unstable angina pectoris and acute myocardial infarction were higher (p less than 0.01) than in patients with stable angina or in control subjects, elevations in peptide B beta 30-43 levels were independent of the differences in both leukocyte count and absolute neutrophil count as well as in history of smoking, hypertension, diabetes mellitus or treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Increased neutrophil elastase release in unstable angina pectoris and acute myocardial infarction. 234 35

Neutrophils contribute to the healing of and scar formation in myocardium after ischemic injury. Many recent studies indicate that neutrophils may be involved in the genesis and propagation of myocardial ischemia. To characterize neutrophil function in ischemic heart disease, neutrophil chemotaxis, leukotriene B4 (LTB4) generation, and elastase release in plasma were measured in 20 patients with stable angina, 17 patients with unstable angina or acute myocardial infarction (AMI), and 20 age-matched control subjects. Neutrophils from patients with stable angina exhibited markedly increased chemotactic activity and LTB4 generation as compared with the age-matched control subjects (p less than 0.01). Neutrophils of nine of 17 patients with unstable angina or AMI clumped spontaneously ex vivo and exhibited marked pseudopod formation and granule extrusion on electron microscopy. Subsequent chemotactic activity and LTB4 generation by neutrophils from these patients was less than in patients with stable angina, suggesting previous in vivo activation. Plasma levels of peptide B beta, a product of fibrin degradation by human neutrophil elastase, were approximately 15-fold higher (p less than 0.001) in patients with unstable angina or AMI (588 +/- 171 pmol/l, mean +/- SEM) compared with those in patients with stable angina (37 +/- 25 pmol/l) or control subjects (40 +/- 22 pmol/l), confirming intense in vivo neutrophil activation. Our study shows enhanced neutrophil function in patients with ischemic heart disease. The increased neutrophil chemotactic activity and LTB4 generation may be markers of stable angina pectoris. Intense neutrophil activation in unstable angina or AMI, as manifested by morphologic changes in neutrophils and elastase release, may relate to ongoing in vivo cellular activation.
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PMID:Neutrophil function in ischemic heart disease. 253 59

Polymorphonuclear neutrophils (PMN) play an important role in myocardial ischemia/reperfusion (MI/R) injury; however, the role of neutrophilic proteases is less understood. The effects of a novel serine protease inhibitor (serpin), LEX032, were investigated in a murine model of MI (20 min) and R (24 hr) injury in vivo. LEX032 is a recombinant human alpha 1-antichymotrypsin in which six amino acid residues were replaced around the active center with those of alpha-1 protease inhibitor. LEX032 has the ability to inhibit both neutrophil elastase and cathepsin G, two major neutral serine proteases in neutrophils, as well as superoxide generation. LEX032 (25 or 50 mg/kg) administered i.v. 1 min before reperfusion significantly attenuated myocardial necrotic injury evaluated by cardiac creatine kinase loss compared to MI/R rats receiving only vehicle (P < .001). Moreover, cardiac myeloperoxidase activity, an index of PMN accumulation, in the ischemic myocardium was significantly attenuated by LEX032 as compared with rats receiving vehicle (P < .001). LEX032 also moderately attenuated leukotriene B4-stimulated PMN adherence to rat superior mesenteric artery endothelium and markedly diminished superoxide radical release from LTB4-stimulated PMN in vitro. In a glycogen-induced rat peritonitis model, LEX032 (50 mg/kg) significantly attenuated PMN transmigration into the peritoneal cavity in vivo. In conclusion, the recombinant serine protease inhibitor, LEX032, appears to be an effective agent for attenuating MI/R injury by inhibiting neutrophil-accumulation into the ischemic-reperfused myocardium and by inactivating cytotoxic metabolites (proteases and superoxide radical) released from neutrophils.
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PMID:Cardioprotection by a novel recombinant serine protease inhibitor in myocardial ischemia and reperfusion injury. 756 95

12 volunteers with slightly elevated serum triglyceride levels were given 30 ml fish oil (5.4 g eicosapentaenoic acid and 3.2 g docosahexaenoic acid) daily for 4 weeks. The percentage of eicosapentaenoic acid increased (P < 0.01) and the percentage of linoleic (P < 0.05) and arachidonic acid (P < 0.01) decreased in neutrophil phospholipids. Superoxide generation by neutrophils initiated by phorbol myristate acetate decreased significantly from 48.6 +/- 8.8 to 34.7 +/- 11.1 nmol/10 min/400,000 cells (means +/- SD, P < 0.01, n = 11). Treatment of the cells with the cyclooxygenase inhibitor indomethacin had no significant influence on the decrease in superoxide generation, indicating that cyclooxygenase products were not involved in this effect of fish oil. Neutrophil elastase release did not change significantly, suggesting that neutrophil lysosomal enzyme release and superoxide generation may be under separate control. In conclusion, dietary fish oil decreased superoxide generation by human neutrophils without involvement of the cyclooxygenase pathway and without altering neutrophil lysosomal enzyme release. Dietary fish oil could have beneficial effects in pathological conditions with activated neutrophils, such as ischaemic heart disease.
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PMID:Dietary fish oil decreases superoxide generation by human neutrophils: relation to cyclooxygenase pathway and lysosomal enzyme release. 893 Nov 14

Transforming growth factor-beta (TGF-beta), interleukin-8 (IL-8), and leukotrienes are potent neutrophil chemoattractants that are released in several lung diseases. There is limited information about the release of TGF-beta in bronchoalveolar lavage fluid (BALF) of patients with pneumonia. Furthermore, it is not clear if TGF-beta is differentially expressed in different lung diseases. The aim of our study was to compare the concentrations of TGF-beta1 and TGF-beta2 in the BALF of patients with pneumonia and other lung diseases. Furthermore, correlation of the TGF-beta levels with the concentration of chemoattractant mediators as well as with indicators of macrophage and granulocyte activation should be investigated. Patients with pneumonia, interstitial lung disease (ILD), or chronic obstructive pulmonary diseases (COPD) were included. Patients with ischemic heart disease without pulmonary involvement served as controls. The concentrations of TGF-beta1 and TGF-beta2, of the chemoattractant cytokine IL-8, of leukotriene B4, and of the leukotrienes C4, D4, and E4 were measured. Neutrophil elastase and granulocyte content (PMN) were used as markers for granulocyte activation, and neopterin was used as a marker for the activation of macrophages. Significantly elevated levels of TGF-beta1 (mean = 0.216 ng/ml, p < 0.01) were found in patients with microbiologically positive pneumonia but not in patients with ILD or COPD. A significant (p < 0.001) correlation was found between the TGF-beta1 concentrations and the IL-8 levels and the percentage of granulocytes (r = 0.76, and r = 0.44, respectively). Elevated TGF-beta2 concentrations were measured in the BALF of patients with pneumonia (mean = 1.4 ng/ml, p < 0.01) and with ILD. Pneumonia was also associated with increased concentrations of leukotrienes C4, D4, and E4 (mean = 91.61 pg/ml, p < 0.05) and leukotriene B4 (mean = 203.9 pg/ml, p < 0.01), significantly elevated levels of PMN elastase (mean = 2958.26 ng/ml, p < 0.01), and neopterin (mean = 0.42 nmol/L). Our results strongly suggest that different lung diseases do differ with regard to the released cytokines. TGF-beta1 probably plays a key role in regulation of pulmonary inflammation, particularly in pneumonia.
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PMID:Increased release of transforming growth factor (TGF)-beta1, TGF-beta2, and chemoattractant mediators in pneumonia. 1021 66

We compared the inflammatory response, hemodilution, and blood loss in patients who underwent mini-cardiopulmonary bypass (CPB) or conventional CPB during coronary artery bypass grafting (CABG). Ninety-eight consecutive patients with ischemic heart disease were randomly assigned to mini-CPB (n = 34) or conventional CPB (n = 64). Interleukin (IL) -8 and neutrophil elastase levels were measured before and after surgery. Hemodilution during CPB, blood loss during and after surgery were also evaluated. Compared with the conventional group, the mini-CPB group had lower levels of IL-8 on postoperative day 1 (8.3 +/- 6.4 vs. 19 +/- 11 pg/mL, p = 0.016) and of neutrophil elastase on postoperative days 1 (127 +/- 52 vs. 240 +/- 100 microg/L, p = 0.013) and 2 (107 +/- 17 vs. 170 +/- 45 micro/L, p = 0.0001). The mini-CPB group also has less blood loss during (620 +/- 595 vs. 978 +/- 658 mL, p = 0.012) and after the operation (578 +/- 310 vs. 1,002 +/- 651 mL, p = 0.0034) and a hemodilution ratio of 14 +/- 2 vs. 25% +/- 3%, p < 0.0001. Thus, mini-CPB attenuated the inflammatory response and hemodilution, resulting in blood conservation in patients undergoing CABG.
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PMID:Beneficial effects of mini-cardiopulmonary bypass on hemostasis in coronary artery bypass grafting: analysis of inflammatory response and hemodilution. 1835 57

Cardiopulmonary bypass may cause acute lung injury and can seriously affect postoperative outcome, especially in younger patients. A synthesized neutrophil elastase inhibitor, sivelestat sodium, may be most effective when used during cardiopulmonary bypass. After anesthesia induction, sivelestat (2 mg/kg/h) was given to the SS group (n=7), and 0.9% saline solution to the placebo group (n=7). Piglets were placed on hypothermic cardiopulmonary bypass and subjected to myocardial ischemia (2 h) induced by cold crystalloid cardioplegia. At 24 h after surgery, PaO(2)/FiO(2) ratio and alveolar-arterial oxygen difference were significantly better in the SS group (379.1+/-93.9 mmHg and 250.5+/-89.3 mmHg) than the placebo group (232.4+/-105.3 mmHg, and 378.3+/-90.8 mmHg, P<0.05). Interleukin-8 level in the epithelial lining fluid was above the lowest standard in 6 out of 7 (4.5, 12.9, 24.6, 27.7, 37.7, and 159.8; mean=44.5+/-57.6 g/l) in the placebo group, and in 2 out of 7 (36.1 and 67.8 g/l) in the SS group (P<0.05). The median histological score of acute lung injury in the harvested lung was 3 (2-5) in the placebo group and 1 (1-5) in the SS group (P<0.05). Intraoperative administration of sivelestat effectively reduced neutrophil induction and activation in the lung and improved oxygenation after cardiopulmonary bypass in a piglet model.
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PMID:The effect of sivelestat sodium on post-cardiopulmonary bypass acute lung injury in a neonatal piglet model. 1859 53

The neutrophil elastase inhibitor sivelestat (ONO-5046) possesses unknown mechanisms of cardioprotection when infused following global ischemia, even in the absence of neutrophils. Since myocardial ischemia-reperfusion injury is strongly associated with endothelial dysfunction and reactive oxygen species (ROS) generation during reperfusion, we have tested the hypothesis that infusion of sivelestat during postischemic low flow would preserve endothelial and contractile function and reduce infarct size through an ROS-mediated mechanism. Isolated male rat hearts, subjected to global ischemia of 25 minutes, were reperfused with low flow with or without sivelestat followed by a full flow reperfusion. Hearts treated with sivelestat showed a significant improvement of LV contractile function and a reduction in infarct size. Infusion of L-NAME (nonspecific blocker of endothelial nitric oxide synthase (eNOS)) along with sivelestat during reperfusion reversed the preservation of contractile function and infarct size. In vitro EPR spin trapping experiments showed that sivelestat treatment decreased superoxide adduct formation in bovine aortic endothelial cells (BAECs) subjected to hypoxia-reoxygenation. Similarly, dihydroethidine (DHE) staining showed decreased superoxide production in LV sections from sivelestat-treated hearts. Taken together, these results indicate that sivelestat infusion during postischemic low flow reduces infarct size and preserves vasoreactivity in association with decreased ROS formation and the preservation of nitric oxide.
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PMID:Sivelestat attenuates myocardial reperfusion injury during brief low flow postischemic infusion. 2376 50


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