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

We previously reported that administration of NO donors ameliorates the severity of myocardial injury in cholesterol-fed rabbits. We now evaluated the effects of probucol, a lipid-lowering antioxidant that can preserve endothelium-dependent relaxation (EDR), in the aortas of cholesterol-fed rabbits. We examined the effects of short-term (7 days) or long-term (24 weeks) administration of 1% probucol on the size of infarcts resulting from 30 minutes of coronary occlusion followed by reperfusion (for 48 hours) in Watanabe heritable hyperlipidemic (WHHL) rabbits. Infarcts in untreated WHHL rabbits were significantly larger than those in the rabbits receiving the long-term but not the short-term treatment with probucol (72.2 +/- 5.4%, 37.6 +/- 6.4%, and 66.7 +/- 3.5%, respectively). Long-term probucol treatment also significantly reduced myeloperoxidase activity in both ischemic and nonischemic myocardium and suppressed P-selectin expression in the coronary vasculature. No significant differences were observed in hemodynamic parameters during myocardial ischemia/reperfusion. Long-term probucol treatment significantly reduced the surface area of atherosclerotic plaque lesions in the aorta (24.4 +/- 3.8% vs 46.3 +/- 6.3, P < .05). Moreover, long-term probucol treatment restored acetylcholine-induced EDR in aortic rings but did not affect sodium nitroprusside-induced relaxation. Finally, long-term probucol treatment resulted in significantly elevated cGMP levels in the aorta. These results indicate that long-term probucol treatment significantly ameliorates myocardial injury in heritable atherosclerotic rabbits, perhaps by reducing the accumulation of leukocytes in the myocardium and atherosclerotic vascular lesions. Thus, long-term administration appears to suppress the progression of atherosclerotic vascular disease in this animal model.
 ...
PMID:Long-term probucol treatment reverses the severity of myocardial injury in watanabe heritable hyperlipidemic rabbits. 940 58

The present study examines whether an acute inflammatory response occurs during acute myocardial infarction (AMI) by measuring soluble P-selectin levels. We examined plasma soluble P-selectin levels in 16 consecutive patients with AMI, in 15 patients with angina, and in 13 control subjects with chest pain but normal coronary arteries and no coronary spasm. In patients with AMI, blood samples were obtained immediately after admission and at 1, 4, 24, and 48 hours, and 1 week after initiation of reperfusion therapy. The plasma soluble P-selectin levels were significantly higher in the AMI group on admission than in the other 2 groups (83 +/- 13 ng/ml, p < 0.01). The plasma soluble P-selectin levels at baseline were not significantly different between the angina and control groups (28 +/- 4 vs 24 +/- 5 ng/ml, p = NS). Plasma soluble P-selectin levels reached their peak significantly at 4 hours after initiation of the reperfusion therapy in patients with AMI. The peak level was significantly higher than the level on admission (115 +/- 17 vs 83 +/- 13 ng/ml, p < 0.05). The plasma soluble P-selectin levels were higher in the AMI group than in the angina and control groups over the time course (p < 0.01). Our data indicate that the plasma soluble P-selectin levels are increased in patients with AMI, and that the levels are increases after reperfusion therapy more than before reperfusion. We suggest that the increase in the plasma soluble P-selectin levels may be caused by the activation of endothelial cells and platelets after myocardial ischemia and reperfusion during AMI.
 ...
PMID:Serial changes in plasma levels of soluble P-selectin in patients with acute myocardial infarction. 948 26

The role of P-selectin and the ligands of selectins such as sialyl Lewis X and sulfatide was studied in a myocardial ischemia and reperfusion injury model. Anesthetized rabbits underwent the occlusion of coronary artery (30 min) followed by reperfusion (5 h). The inhibitory effect on myocardial ischemia and reperfusion injury was examined with infarct size normalized by area-at-risk. Intravenous administration of an anti-P-selectin monoclonal antibody, PB1.3 (2 mg/kg), reduced infarct size by 38%. Similarly, the administration of sialyl Lewis X-oligosaccharide (10 mg/kg) reduced infarct size by 53% significantly. Finally, the infarct size was significantly reduced bv 39% in sulfatide-treated group (10 mg/kg). These results suggest that P-selectin plays an important role in myocardial ischemia and reperfusion injury and that the ligands of selectins, such as sialyl Lewis X-oligosaccharide and sulfatide, have cardioprotective effect on myocardial ischemia and reperfusion injury.
 ...
PMID:The role of P-selectin, sialyl Lewis X and sulfatide in myocardial ischemia and reperfusion injury. 965 63

Myocardial injury after ischemia (I) and reperfusion (R) is related to leukocyte activation with subsequent release of cytokines and oxygen-derived free radicals as well as complement activation. In our study, the cardioprotective effects of exogenous C1 esterase inhibitor (C1 INH) were examined in a rat model of myocardial I + R (i.e., 20 min + 24 hr or 48 hr). The C1 INH (10, 50 and 100 U/kg) administered 2 min before reperfusion significantly attenuated myocardial injury after 24 hr of R compared to vehicle treated rats (P < .001). Further, cardiac myeloperoxidase activity (i.e., a marker of PMN [polymorphonuclear leukocyte] accumulation) in the ischemic area was significantly reduced after C1 INH treatment compared to vehicle treated animals (0.81 +/- 0.1, 0.34 +/- 0.13, 0.13 +/- 0.1 vs. 1.44 +/- 0.3 U/100 mg tissue, P < .001). In addition, C1 INH (100 U/kg) significantly attenuated myocardial injury and neutrophil infiltration even after 48 hr of reperfusion compared to vehicle treatment. Immunohistochemical analysis of ischemic-reperfused myocardial tissue demonstrated activation of classical complement pathway by deposition of C1q on cardiac myocytes and cardiac vessels. In addition, expression of the endothelial adhesion molecules P-selectin and intercellular adhesion molecule 1 (ICAM-1) was observed after reperfusion of the ischemic myocardium. In this regard, C1 INH administration abolished expression of P-selectin and ICAM-1 on the cardiac vasculature after myocardial ischemia and reperfusion. Blocking the classical complement pathway by exogenous C1 INH appears to be an effective means to preserve ischemic myocardium from injury after 24 and 48 hr of reperfusion. The mechanisms of this cardioprotective effect appears to be due to blocking of complement activation and reduced endothelial adhesion molecule expression with subsequent reduced PMN-endothelium interaction, resulting in diminished cardiac necrosis.
 ...
PMID:Blocking of classical complement pathway inhibits endothelial adhesion molecule expression and preserves ischemic myocardium from reperfusion injury. 965 88

The nuclear enzyme poly (ADP-ribose) synthetase (PARS) has been shown to play an important role in the pathogenesis of ischemia/reperfusion injury and circulatory shock. The aim of this study was to investigate whether PARS activity may modulate endothelial-neutrophil interaction. We present evidence that genetic disruption of PARS provides protection against myocardial ischemia and reperfusion injury by inhibiting the expression of P-selectin and intercellular adhesion molecule-1 (ICAM-1) and, consequently, by inhibiting the recruitment of neutrophils into the jeopardized tissue. Furthermore, using in vitro studies, we demonstrate that in fibroblasts lacking a functional gene for PARS, cytokine-stimulated expression of ICAM-1 is significantly reduced compared with fibroblasts from animals with a normal genotype. Similarly, in cultured human endothelial cells, oxidative- or cytokine-dependent expression of P-selectin and ICAM-1 is reduced by pharmacological inhibition of PARS by 3-aminobenzamide. These findings provide the first direct evidence that PARS activation participates in neutrophil-mediated myocardial damage by regulating the expression of P-selectin and ICAM-1 in ischemic and reperfused myocardium, and they also provide the basis for a novel therapeutic approach for the treatment of reperfusion injury.
 ...
PMID:Genetic disruption of poly (ADP-ribose) synthetase inhibits the expression of P-selectin and intercellular adhesion molecule-1 in myocardial ischemia/reperfusion injury. 967 Sep 21

Peroxynitrite (ONOO-), an intermediate formed from the equimolar interaction of nitric oxide (NO) and superoxide, is thought to be an important mediator of tissue injury in myocardial ischemia-reperfusion. However, physiologically relevant (i.e., maximally achievable) concentrations of ONOO- significantly decreased neutrophil-endothelium interactions in the rat mesentery. We therefore examined the dose-response relationship of infusion of different concentrations of ONOO- in a feline model of myocardial ischemia-reperfusion and provide data on the cellular mechanisms responsible for these observed effects. Cats subjected to 90 min of ischemia followed by 270 min of reperfusion were infused with different concentrations of ONOO- 10 min before reperfusion and continuing throughout reperfusion. We observed that infusion of 2 microM ONOO- provided significant cardioprotection, whereas either 0.2 or 20 microM ONOO- did not protect. ONOO- at 2 microM also preserved coronary endothelial function, decreased P-selectin expression, and attenuated polymorphonuclear leukocyte (PMN) adherence to the vascular endothelium. ONOO- did not exert its cardioprotective effects by acting as a direct NO donor in solution. However, in vitro, ONOO- can react with glutathione to form S-nitrosoglutathione, which can act as an NO carrier and exert beneficial effects. Thus only maximally achievable concentrations of ONOO- exert significant cardioprotective effects, in part by decreasing surface expression of P-selectin and decreasing PMN-endothelium interactions.
 ...
PMID:Mechanisms of cardioprotection by peroxynitrite in myocardial ischemia and reperfusion injury. 968 39

The acute coronary syndromes represent a continuum of myocardial ischemia ranging from angina, reversible tissue injury --> unstable angina, frequently associated with minor myocardial damage --> myocardial infarction and extensive tissue necrosis. Historically, coronary artery disease assessment has been mainly binary, using WHO criteria of symptoms, electrocardiography, and biochemical markers. The creatine kinase-MB isoenzyme (CK-MB) has been a benchmark for markers, but it is not specific for myocardium. Cardiac-specific isoforms of troponin T and I have emerged as sensitive myocardial infarction (MI) indicators and, importantly, for risk stratification of acute coronary syndrome patients. In addition to markers of myocardial cell necrosis, markers of plaque disruption (C-reactive protein and serum amyloid A), "angry" platelets (P-selectin), ischemia (glycogen phosphorylase-BB isoenzyme), and the procoagulant state and thrombosis (soluble fibrin) have potential use. Also, CK-MB and myoglobin have been combined with clinical indicators for monitoring reperfusion after thrombolytic therapy. Biochemical markers will continue to be an important clinical adjunct for MI diagnosis, risk assessment, and reperfusion monitoring in the future.
 ...
PMID:Biochemical markers of the acute coronary syndromes. 970 95

We investigated in vivo coronary P-selectin expression and its pathophysiological consequences in a murine model of myocardial ischemia-reperfusion (MI/R) using wild-type and P-selectin deficient (-/-) mice. Coronary P-selectin expression [microgram monoclonal antibody (MAb)/g tissue] was measured using a radiolabeled MAb method after 30 min of myocardial ischemia and 20 min of reperfusion. P-selectin expression in wild-type mice was significantly (P < 0. 01) elevated in the ischemic zone (0.070 +/- 0.010) compared with the nonischemic zone (0.037 +/- 0.008). Myocardial P-selectin expression was nearly undetectable in P-selectin -/- mice after MI/R. Furthermore, myocardial infarct size (% of area at risk) after 30 min of myocardial ischemia and 120 min of reperfusion was 42.5 +/- 4. 4 in wild-type mice and 24.4 +/- 4.0 in P-selectin -/- mice (P < 0. 05). In additional experiments of prolonged myocardial ischemia (60 min) and reperfusion (120 min), myocardial infarct size was similar in P-selectin -/- mice and wild-type mice. Our results clearly demonstrate the involvement of coronary P-selectin in the development of myocardial infarction after MI/R.
 ...
PMID:Coronary endothelial P-selectin in pathogenesis of myocardial ischemia-reperfusion injury. 981 95

Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction as well as myocardial injury. These effects are due in large part to endothelial dysfunction leading to an upregulation of cell adhesion molecules and subsequent neutrophil induced cardiac injury. The proteasome inhibitor, PS-519, has been shown to attenuate leukocyte-endothelial cell interactions. We tested the effects of PS-519 on neutrophil mediated cardiac dysfunction in ischemia/reperfusion. This study examines the effects of PS-519 in a neutrophil dependent isolated perfused rat heart model of ischemia (I) (20 min) and reperfusion (R) (45 min). Administration of PS-519 (0.01, 0.1, 0.3, 1.0 mg/kg) to I/R hearts perfused with PMNs improved coronary flow, and preserved left ventricular developed pressure (LVDP) and + dP/dt max as indices of cardiac contractile function. At 1.0 mg/kg, PS-519 treated hearts exhibited a final LVDP of 98 +/- 3% of initial compared to 52 +/- 8% in I/R hearts receiving only vehicle (P < 0.001). In addition, PS-519 significantly reduced PMN accumulation in the ischemic myocardium from 25.1 +/- 2.1 PMNs/mm2 in untreated hearts to 7.3 PMNs/mm2, and attenuated P-selectin surface expression on coronary vascular endothelium from 7.1 +/- 0.3% to 1.4 +/- 0.2% (P < 0.01). These results provide evidence that PS-519 is a potent and effective cardioprotective agent that inhibits P-selectin leukocyte-endothelial cell interactions and preserves cardiac contractile function and coronary perfusion following myocardial ischemia and reperfusion.
 ...
PMID:Cardioprotective effects of a novel proteasome inhibitor following ischemia and reperfusion in the isolated perfused rat heart. 1009 58

Myocardial ischemia and reperfusion (MI/R) initiates a cascade of polymorphonuclear neutrophil (PMN)-mediated injury, the magnitude of which may be influenced by the bioavailability of nitric oxide (NO). We investigated the role of endothelial cell nitric oxide synthase (ecNOS) in MI/R injury by subjecting wild-type and ecNOS-deficient (-/-) mice to 20 min of coronary artery occlusion and 120 min of reperfusion. Myocardial infarct size represented 20.9 +/- 2.9% of the ischemic zone in wild-type mice, whereas the ecNOS -/- mice had significantly (P < 0.01) larger infarcts measuring 46.0 +/- 3.8% of the ischemic zone. Because P-selectin is thought to be involved with the pathogenesis of neutrophil-mediated I/R injury, we assessed the effects of MI/R on P-selectin expression in the myocardium of wild-type and ecNOS -/- mice. P-selectin expression measured with a radiolabeled monoclonal antibody (MAb) technique after MI/R in wild-type mice was 0.037 +/- 0.009 microgram MAb/g tissue, whereas ecNOS -/- coronary vasculature was characterized by significantly (P < 0.05) higher P-selectin expression (0.080 +/- 0.013 microgram MAb/g tissue). Histological examination of the postischemic myocardium revealed significantly (P < 0.01) more neutrophils in the ecNOS -/- (29.5 +/- 2.5 PMN/field) compared with wild-type (5.0 +/- 0.9 PMN/field) mice. A similar trend in infarct size and neutrophil accumulation was observed when wild-type and ecNOS -/- mice were subjected to 30 min of ischemia and 120 min of reperfusion. These novel in vivo findings demonstrate a cardioprotective role for ecNOS-derived NO in the ischemic-reperfused mouse heart.
 ...
PMID:Myocardial ischemia-reperfusion injury is exacerbated in absence of endothelial cell nitric oxide synthase. 1033 Feb 40


<< Previous 1 2 3 4 5 6 7 Next >>