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)

Under effects of myocardial ischemia (30 min), the activities of the intermembrane enzymes of rabbit heart mitochondria, i.e., adenylate kinase and creatine kinase, are inhibited by 20% and 23%, respectively. Consequently, the creatine- and AMP-activated respiration of mitochondria diminishes by 52% and 39%, respectively. An inhibitory analysis of ADP-, AMP- and creatine-activated mitochondrial respiration performed in the presence of atractyloside has demonstrated that ischemia (30 min), adriblastin (0.688 mM) and succinate (10 mM) cause alterations in the functional coupling of adenylate kinase and creatine kinase with the adenine nucleotide translocator. These alterations lead to the diminution of the rate and efficiency of energy transfer from mitochondria to hexokinase, as an arbitrary site of energy consumption. An addition of cytochrome c to ischemic heart mitochondria results in an increase in the rate of ATP synthesis; however, the efficiency of this process is lowered. The toxic effect of the anticancer drug--adriblastin on heart mitochondria respiration is enhanced in the presence of creatine in the bathing solution.
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PMID:[Functional changes in the mitochondrial site of adenylate kinase and creatine kinase systems of energy transport induced by myocardial ischemia and adriablastin]. 284 Jan 29

Differential cytochrome spectra and their fourth degree derivatives were recorded at 77 degrees K temperature. During myocardial ischemia (2-h autolysis), only cytochrome c content was found to be decreased in isolated mitochondria. According to these data mitochondrial state 3 respiration with succinate decreased only in a medium without cytochrome c. Before ADP addition mitochondrial respiration increased but in a medium with cytochrome c. This was followed by an increase in the respiration rate minimized by bromthymole blue, an inhibitor of dicarboxylate transport. It is inferred that these alterations seen in ischemia are linked with increased permeability of mitochondrial membranes: external for cytochrome c, and internal for inorganic ions and low-molecular compounds.
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PMID:[Changes in the quantitative composition of cytochromes and the functional activity of heart mitochondria during ischemia]. 631 61

Because myocardial ischemia is correlated with both an elevation of intracellular levels of amphiphilic lipid metabolites and a decrease in the rotenone-insensitive NADH cytochrome c reductase (RINCR), we investigated the effects in vitro of some amphiphilic lipid metabolites and synthetic detergents on the activity of RINCR-enriched subfractions of microsomes from isolated cardiac myocytes. RINCR activity was unaffected in vitro by the addition of lysophosphatidylethanolamine (up to 0.5 mM) but was inhibited (maximum 63%) by lysophosphatidylcholine (8 microM). Palmitoyl carnitine (up to 2 mM) was ineffective, but the coenzyme A thioesters of palmitate, stearate, oleate, and arachidonate were inhibitory at concentrations (less than 3 microM) below their critical micellar concentrations. Arachidonyl CoA was approximately one order of magnitude more inhibitory than the other long-chain acyl CoA thioesters. Kinetic analyses revealed the effect of arachidonyl CoA on RINCR activity to be exclusively an alteration of the Vmax with no change in the Km for cytochrome c. The inhibition of myocytic RINCR activity by long-chain acyl CoA may be unrelated to the bulk-phase detergency of this lipid amphiphile since the effects were observed at concentrations below the critical micellar concentration, and other lipid amphiphiles had no effect on RINCR activity. Inhibition of microsomal RINCR activity may result from localized disruption of the membrane microenvironment of the enzyme complex by penetration or dissolution of long-chain acyl CoA into the membrane. The pronounced sensitivity of myocytic RINCR activity to long-chain acyl CoA suggests a relationship between the decreased RINCR activity and the increased levels of this class of lipid metabolites observed in the ischemic myocardium.
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PMID:Inhibition of myocardial rotenone-insensitive NADH cytochrome c reductase by amphiphilic compounds. 650 37

The effect of myocardial ischemia on mitochondrial oxidative phosphorylation was investigated using isolated, buffer-perfused rabbit hearts. After 45 min of global ischemia, oxidative phosphorylation was decreased only in the subsarcolemmal population of mitochondria with all substrates tested. The oxidation of N,N,N',N' tetramethyl p-phenylenediamine-ascorbate, an electron donor to cytochrome oxidase via cytochrome c, was decreased in subsarcolemmal mitochondria [ischemia (n = 6): 76 +/- 3 vs. control (n = 5): 105 +/- 6 nanoatoms O.min-1.mg-1, P < 0.01] but not in interfibrillar mitochondria. Only minor morphological changes were observed by electron microscopy in the isolated mitochondria after ischemia. Neither cytochrome oxidase activity measured under conditions for maximal activity nor the apparent Michaelis constant and maximum velocity values of the two cytochrome c binding sites were different in subsarcolemmal mitochondria isolated from ischemic and control hearts. The cytochrome c content was decreased in subsarcolemmal mitochondria after ischemia (ischemia: 0.111 +/- 0.013 vs. control: 0.156 +/- 0.007 nmol/mg protein, P < 0.05). Thus ischemia decreased the rate of oxidative phosphorylation through cytochrome oxidase selectively in intact subsarcolemmal mitochondria. Ischemic damage to the terminal segment of the electron transport chain involves a decrease in the content of cytochrome c, whereas the expressible catalytic activity of cytochrome oxidase remains unchanged.
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PMID:Myocardial ischemia decreases oxidative phosphorylation through cytochrome oxidase in subsarcolemmal mitochondria. 932 48

The cardioprotective effect of cytochrome c preparations was evaluated according to the test for restriction of the size of the myocardial infarct and the effect on the course of acute myocardial ischemia in acute experiments on dogs. Cytochrome c of biotechnological and animal origin and hemtetradecapeptide caused a marked decrease in the size of the myocardial necrosis in experiments on rats: from 68 +/- 4.3% in the control to 32 +/- 3.4, 46 +/- 8.3 and 44 +/- 4.7%, respectively. In dog experiments the cytochrome c agents reduced the intensity of dp/dt decline and decreased the collateral coronary blood flow in acute myocardial ischemic. They produced a beneficial effect on heart bioenergetics, namely, reduced the lactate level in blood flowing from the zone of the ischemia and glucose consumption by the ischemic myocardium. The cardioprotective effect of biotechnological cytochrome c hemtetradecapeptide was practically identical to the effect of the enzyme of animal origin.
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PMID:[The cardioprotective action of preparations of biotechnological cytochrome c in acute myocardial ischemia]. 962 Nov 69

Myocardial ischemia/reperfusion is well recognized as a major cause of apoptotic or necrotic cell death. Neonatal rat cardiac myocytes are intrinsically resistant to hypoxia-induced apoptosis, suggesting a protective role of energy-generating substrates. In the present report, a model of sustained hypoxia of primary cultures of Percoll-enriched neonatal rat cardiac myocytes was used to study specifically the modulatory role of extracellular glucose and other intermediary substrates of energy metabolism (pyruvate, lactate, propionate) as well as glycolytic inhibitors (2-deoxyglucose and iodoacetate) on the induction and maintenance of apoptosis. In the absence of glucose and other substrates, hypoxia (5% CO2 and 95% N2) caused apoptosis in 14% of cardiac myocytes at 3 h and in 22% of cells at 6-8 h of hypoxia, as revealed by sarcolemmal membrane blebbing, nuclear fragmentation, and chromatin condensation (Hoechst staining), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and DNA laddering. This was accompanied by translocation of cytochrome c from the mitochondria to the cytosol and cleavage of the death substrate poly(ADP-ribose) polymerase. Cleavage of poly(ADP-ribose) polymerase and DNA laddering were prevented by preincubation with the caspase inhibitors benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVAD-fmk) and benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethyl ketone (zDEVD-fmk), indicating activation of caspases in the apoptotic process. The caspase inhibitor zDEVD-fmk also partially inhibited cytochrome c translocation. The presence of as little as 1 mM glucose, but not pyruvate, lactate, or propionate, before hypoxia prevented apoptosis. Inhibiting glycolysis by 2-deoxyglucose or iodoacetate, in the presence of glucose, reversed the protective effect of glucose. This study demonstrates that glycolysis of extracellular glucose, and not other metabolic pathways, protects cardiac myocytes from hypoxic injury and subsequent apoptosis.
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PMID:Glucose uptake and glycolysis reduce hypoxia-induced apoptosis in cultured neonatal rat cardiac myocytes. 1021 35

Apoptosis has been implicated in ischemic heart disease, but its mechanism in cardiomyocytes has not been elucidated. In this study, we investigate the effects of hypoxia and reoxygenation in adult cardiomyocytes and the molecular mechanism involved in cardiomyocyte apoptosis. Morphologically, reoxygenation induced rounding up of the cells, appearance of membrane blebs that were filled with marginated mitochondria, and ultrastructural findings characteristic of apoptosis. Reoxygenation (18 hours of reoxygenation after 6 hours of hypoxia) and prolonged hypoxia (24 hours of hypoxia) resulted in a 59% and 51% decrease in cellular viability, respectively. During reoxygenation, cell death occurred predominantly via apoptosis associated with appearance of cytosolic cytochrome c and activation of caspase-3 and -9. However, nonapoptotic cell death predominated during prolonged hypoxia. Both caspase inhibition and Bcl-2 overexpression during reoxygenation significantly improved cellular viability through inhibition of apoptosis but had minimal effect on hypoxia-induced cell death. Bcl-2 overexpression blocked reoxygenation-induced cytochrome c release and activation of caspase -3 and -9, but caspase inhibition alone did not block cytochrome c release. These results suggest that apoptosis predominates in cardiomyocytes after reoxygenation through a mitochondrion-dependent apoptotic pathway, and Bcl-2 prevents reoxygenation-induced apoptosis by inhibiting cytochrome c release from the mitochondria and prevents activation of caspase-3 and -9.
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PMID:Morphological and molecular characterization of adult cardiomyocyte apoptosis during hypoxia and reoxygenation. 1090 95

Previous studies have suggested that oxygen-derived free radicals are involved in the pathophysiology of myocardial ischemia/reperfusion (MI/R) injury. Specifically, neutrophils have been shown to mediate postischemic ventricular arrhythmias and myocardial necrosis. We hypothesized that MI/R injury would be reduced in the absence (-/-) of NADPH oxidase. Heterozygous control mice (n=23) and NADPH oxidase(-/-) mice (n=24) were subjected to 30 minutes of coronary artery occlusion and 24 hours of reperfusion. Myocardial area at risk per left ventricle was similar in heterozygous control hearts (55+/-3%) and NADPH oxidase(-/-) hearts (61+/-4%). Contrary to our hypothesis, the size of infarct area at risk was similar in the heterozygous control mice (42+/-4%) and NADPH oxidase(-/-) mice (34+/-5%) (P=not significant). In addition, echocardiographic examination of both groups revealed that left ventricle fractional shortening was similar in NADPH oxidase(-/-) mice (n=8; 27+/-2.5%) and heterozygous control mice (n=10; 23.3+/-3. 3%) after MI/R. Superoxide production, as detected by cytochrome c reduction, was significantly impaired (P<0.01) in NADPH oxidase(-/-) mice (n=6) compared with heterozygous mice (n=7) (0.04+/-0.03 versus 2.2+/-0.08 nmol O(2).min(-1).10(6) cells(-1)). Intravital microscopy of the inflamed mesenteric microcirculation demonstrated that leukocyte rolling and adhesion were unaffected by the absence of NADPH oxidase. Oyster glycogen-stimulated neutrophil transmigration into the peritoneum was also similar in both the heterozygous control mice and NADPH oxidase(-/-) mice (P:=not significant). These findings suggest that NADPH oxidase does not contribute to the development of myocardial injury and dysfunction after MI/R.
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PMID:Myocardial ischemia/reperfusion injury in NADPH oxidase-deficient mice. 1105 86

Reperfusion after myocardial ischemia is associated with a rapid influx of calcium, leading to activation of various enzymes including calpain. Isolated perfused adult rabbit hearts subjected to global ischemia and reperfusion were studied. Calpain or a calpain-like activity was activated within 15 min after reperfusion, and preconditioning suppressed calpain activation. In contrast, caspase activation was not detected although cytochrome c was released after ischemia and reperfusion. The pro-apoptotic BH3-only Bcl-2 family member, Bid, was cleaved during ischemia/reperfusion in the adult rabbit heart. Recombinant Bid was cleaved by calpain to a fragment that was able to mediate cytochrome c release. The calpain cleavage site was mapped to a region within Bid that is extremely susceptible to proteolysis. These findings suggest that there is cross-talk between apoptotic and necrotic pathways in myocardial ischemia/reperfusion injury.
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PMID:Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion. 1140 57

Myocardial depression can be demonstrated following administration of endotoxin. Proposed mechanisms of endotoxin-induced myocardial dysfunction include the release of proinflammatory mediators, focal myocardial ischemia, and the presence of activated leukocytes within the myocardium. Recently, myocardial caspase activation and mitochondria-related apoptotic events (i.e., release of cytochrome c) were demonstrated in the failing septic heart. Here, we tested the hypothesis that immunosuppressors, cyclosporin A and tacrolimus (FK 506), would improve inflammation, heart nuclear apoptosis, and myocardial dysfunction in endotoxin-treated rats. Myocardial contractility was assessed using an isolated heart preparation. Heart leukocyte infiltration was assessed by measurement of heart myeloperoxidase activity. Leukocyte activation was studied using the intravital microscopy of the mesenteric venule. Apoptosis was detected as myocardial DNA fragmentation, downstream caspase activation, and mitochondrial cytochrome c release. Both cyclosporin A and FK 506 reduced heart leukocyte sequestration and venular adhesion in endotoxin-treated rats. Cyclosporin A, which blocks mitochondrial cytochrome c release, was able to reduce endotoxin-induced myocardial end-stage nuclear apoptosis and heart dysfunction, whereas tacrolimus had no such effects. These effects could be related to the unique properties of cyclosporin A to act on mitochondria.
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PMID:Protective effects of cyclosporin A from endotoxin-induced myocardial dysfunction and apoptosis in rats. 1185 Mar 35


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