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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Myocardial stunning, defined as a reversible decrease in contractility after ischemia and reperfusion, may be a manifestation of reperfusion injury caused by free oxygen radical damage. The aim of this study was to test the hypothesis that pretreatment with coenzyme Q10 (ubiquinone), believed to act as a free radical scavenger, reduces myocardial stunning in a porcine model. Twelve swine were randomized to receive either oral supplementation with coenzyme Q10 or placebo for 20 days. A normothermic open-chest model was used with short occlusion (8 min) of the distal left descending coronary artery followed by reperfusion. Regional contractile function was measured with epicardial Doppler crystals in ischemic and nonischemic segments by measuring thickening fraction of the left ventricular wall during systole. Stunning time was defined as the elapsed time of reduced contractility until return to baseline. Coenzyme Q10 concentrations were measured in blood and homogenized myocardial tissue by high performance liquid chromatography. Plasma levels of reduced coenzyme Q10 (ubiquinol) were higher in swine pretreated with the experimental medication as compared to placebo (mean 0.45 mg/l versus 0.11 mg/l, respectively). Myocardial tissue concentrations, however, did not show any changes (mean 0.79 micrograms/mg dry weight versus 0.74 micrograms/mg). Stunning time was significantly reduced in coenzyme Q10 pretreated animals (13.7 +/- 7.7 min versus 32.8 +/- 3.1 min, P < 0.01). In conclusion, chronic pretreatment with coenzyme Q10 protects ischemic myocardium in an open-chest swine model. The beneficial effect of coenzyme Q10 on myocardial stunning may be due to protection from free radical mediated reperfusion injury. This protective effect seems to be generated by a humoral rather than intracellular mechanism.
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PMID:Coenzyme Q10 protects ischemic myocardium in an open-chest swine model. 824 92

The present study set out to investigate whether plasma phosphatidylcholine hydroperoxide (PCOOH) levels could accurately reflect lipid peroxidation linking to liver damage due to ischemia--reperfusion. PCOOH is a primary peroxidative product of phosphatidylcholine (PC), which is the most important functional lipid in the hepatocellular membrane, and may mediate oxidative stress. We quantified PCOOH and PC in the plasma and liver of rats subjected to hepatic ischemia-reperfusion by chemiluminescence detecting HPLC (CL-HPLC) method. Plasma PCOOH levels showed no significant rise in either the ischemia only group or in the sham-operation group, compared to controls (0.7 nmol/mL plasma). At 60 min subsequent to reperfusion, the PCOOH levels in plasma and liver, as well as the levels of several serum markers of liver injury [lactic dehydrogenase (LDH), glutamic-oxalacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT)] increased in proportion to the duration of ischemia (up to 60 min). During periods of reperfusion following 30 min of ischemia, plasma PCOOH increased biphasically (2 nmol/mL; 12-24 hr duration of reperfusion), and generally ran parallel to that in the liver after more than 60 min of reperfusion. Dose-dependent protective effects against warm ischemia (30 min)-reperfusion (12 hr) injury were clearly demonstrated in the groups treated with allopurinol, diclofenac Na, ascorbic acid (V.C), alpha-tocopherol and coenzyme Q10, but not in those treated with r-h-superoxide dismutase or betamethasone. The rises in plasma PCOOH and serum GOT, GPT and LDH of the ischemia-reperfused rats were ameliorated most in the group pretreated with diclofenac Na, and next most in the group pretreated with V.C. These results indicate that the plasma PCOOH levels are a useful index both for liver cell damage induced by oxygen free radicals generated during ischemia-reperfusion, and to investigate the efficacy of drugs against oxidative stress.
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PMID:Effects of anti-free radical interventions on phosphatidylcholine hydroperoxide in plasma after ischemia-reperfusion in the liver of rats. 825 Sep 60

EPR spectroscopy was used to measure paramagnetic species in rat hearts freeze-clamped during control perfusion by the Neely procedure, after 25 min of normothermic global ischemia or 20 min of total reperfusion with oxygenated perfusate. The analysis of spectral and relaxation parameters measured at -40 degrees C showed that in all three cases free radicals in heart tissue were semiquinones of CoQ10 and flavins. Ischemia increased the amount of free radical species (mostly flavosemiquinones) in myocardium about two times, the beginning of reflow of perfusate resulted in decrease of the intensity of the EPR signal to an initial level. The saturation curves were different for control, ischemic and reoxygenated postischemic samples, and they demonstrated the heterogeneity of free radical centers in cardiac mitochondria.
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PMID:[Free radical centers in isolated rat heart tissue in a normal state, in ischemia, and reperfusion]. 838 1

1. Effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, pravastatin and simvastatin, on the myocardial level of coenzyme Q10, and on mitochondrial respiration were examined in dogs. 2. Either vehicle (control), pravastatin (4 mg kg-1 day-1), or simvastatin (2 mg kg-1 day-1) was administered orally for 3 weeks. First, the myocardial tissue level of coenzyme Q10 was determined in the 3 groups. Second, ischaemia was induced by ligating the left anterior descending coronary artery (LAD) in anaesthetized open chest dogs, pretreated with the inhibitors. After 30 min of ischaemia, nonischaemic and ischaemic myocardium were removed from the left circumflex and LAD regions, respectively, and immediately used for isolation of mitochondria. The mitochondrial respiration was determined by polarography, with glutamate and succinate used as substrates. 3. Simvastatin significantly decreased the myocardial level of coenzyme Q10, but pravastatin did not. 4. Ischaemia decreased the mitochondrial respiratory control index (RCI) in both groups. Significant differences in RCI between nonischaemic and ischaemic myocardium were observed in the control and simvastatin-treated groups. 5. Only in the simvastatin-treated group did ischaemia significantly decrease the ADP/O ratio, determined with succinate. 6. The present results indicate that simvastatin but not pravastatin may cause worsening of the myocardial mitochondrial respiration during ischaemia, probably because of reduction of the myocardial coenzyme Q10 level.
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PMID:Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischaemic dog hearts. 852 76

Coenzyme Q10, which is involved in mitochondrial adenosine triphosphate production, is also a powerful antioxidant. We hypothesize that coenzyme Q10 pretreatment protects myocardium from ischemia reperfusion injury both by its ability to increase aerobic energy production and by protecting creatine kinase from oxidative inactivation during reperfusion. Isolated hearts (six per group) from rats pretreated with either coenzyme Q10, 20 mg/kg intramuscularly and 10 mg/kg intraperitoneally (treatment) or vehicle only (control) 24 and 2 hours before the experiment were subjected to 15 minutes of equilibration, 25 minutes of ischemia, and 40 minutes of reperfusion. Developed pressure, contractility, compliance, myocardial oxygen consumption, and myocardial aerobic efficiency were measured. Phosphorus 31 nuclear magnetic resonance (31P-NMR) spectroscopy was used to determine adenosine triphosphate and phosphocreatine concentrations as a percentage of a methylene diphosphonic acid standard. Hearts were assayed for myocardial coenzyme Q10 and myocardial creatine kinase activity at end equilibration and at reperfusion. Treated hearts showed higher myocardial coenzyme Q10 levels (133 +/- 5 micrograms/gm ventricle versus 117 +/- 4 micrograms/gm ventricle, p < 0.05). Developed pressure at end reperfusion was 62% +/- 2% of equilibration in treatment group versus 37% +/- 2% in control group, p < 0.005. Preischemic myocardial aerobic efficiency was preserved during reperfusion in treatment group (0.84 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) vs 1.00 +/- 0.08 mm Hg/(microliter O2/min/gm ventricle) at equilibration, p = not significant), whereas in the control group it fell to 0.62 +/- 0.07 mm Hg/(microliter O2/min/gm ventricle, p < 0.05 vs equilibration and vs the treatment group at reperfusion. Treated hearts showed higher adenosine triphosphate and phosphocreatine levels during both equilibration (adenosine triphosphate 49% +/- 2% for the treatment group vs 33% +/- 3% in the control group, p < 0.005; phosphocreatine 49% +/- 3% in the treatment group vs 35% +/- 3% in the control group, p < 0.005) and reperfusion (adenosine triphosphate 18% +/- 3% in the treatment group vs 11% +/- 2% in the control group, CTRL p < 0.05; phosphocreatine 45% +/- 2% in the treatment group vs 23% +/- 3% in the control group, p < 0.005). Creatine kinase activity in treated hearts at end reperfusion was 74% +/- 3% of equilibration activity vs 65% +/- 2% in the control group, p < 0.05). Coenzyme Q10 pretreatment improves myocardial function after ischemia and reperfusion. This results from a tripartite effect: (1) higher concentration of adenosine triphosphate and phosphocreatine, initially and during reperfusion, (2) improved myocardial aerobic efficiency during reperfusion, and (3) protection of creatine kinase from oxidative inactivation during reperfusion.
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PMID:Elucidation of a tripartite mechanism underlying the improvement in cardiac tolerance to ischemia by coenzyme Q10 pretreatment. 858 19

Platelet aggregation and plasma serotonin were studied during ischemia-reperfusion of the small intestine in dogs. Blood was withdrawn from the superior mesenteric vein before and 1 h after ischemia, then 5, 30 and 60 min after reperfusion. Dipyridamole (5 mg/kg body weight) and coenzyme Q10 (CoQ10; 10 mg/kg body weight) were administered intravenously 5 min before reperfusion, following 1 h ischemia, in order to investigate their effects on platelet function and free serotonin. Ischemia-reperfusion resulted in an increased local free serotonin concentration together with an enhanced platelet response to ADP, collagen and arachidonic acid. Administration of dipyridamole and CoQ10 prior to reperfusion prevented, at least in part, augmented platelet activation and serotonin release. It appeared that dipyridamole was more potent than CoQ10. Our results may indicate a possible protective effect of dipyridamole on enhanced platelet activation during ischemia-reperfusion in dogs.
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PMID:Plasma serotonin and platelet aggregation during ischemia-reperfusion in dogs: effect of dipyridamole and coenzyme Q10. 869 77

The purpose of the present study was to elucidate the effect of hepatic reflow following ischemia on the remnant liver after hepatectomy with occluded hepatic blood inflow in dogs with obstructive jaundice. When 40% hepatectomy was performed with 10-min occlusion of hepatic blood inflow in dogs with obstructive jaundice, the lipid peroxide content in the remnant liver increased significantly, together with a reduction in superoxide dismutase (SOD)-like activity. The levels of endotoxin and beta-N-acetyl hexosaminase (NAH) in peripheral blood also increased. The phagocytic index increased transiently after 30 min, followed by a marked decrease after 3h. Histologically, degeneration and necrosis of the hepatic parenchymal cells were demonstrated, and survival rate at 7 days was only 23.1%. With the administration of coenzyme Q10 (CoQ10) or styrene-co-maleic acid SOD (SM-SOD), these phenomena were significantly inhibited, and the survival rate improved. After hepatectomy, Kupffer cells in the remnant liver were activated by increased endotoxin levels in the portal vein, inducing the production of free radicals, which, in turn, damaged the Kupffer cells by reducing endotoxin clearance. Finally, the impaired functional reserve in the remnant liver provoked liver failure. The administration of CoQ10 or SM-SOD prevented the occurrence of these phenomena triggered by the free radicals generated by Kupffer cells, stimulated by endotoxin in the portal vein.
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PMID:Pathophysiological effect of hepatic ischemia and reperfusion after hepatectomy in dogs with obstructive jaundice, focusing on the effect of coenzyme Q10 and styrene-co-maleic acid superoxide dismutase. 872 30

Coenzyme Q10 (CoQ10, ubiquinone) has been shown to be protective against myocardial ischemia/reperfusion induced injury. The purpose of this study was to investigate the effect of CoQ10 added to cold cristalloid cardioplegia on hypothermic ischemia and normothermic reperfusion using an isolated working rat heart. Hearts (n = 6-9/group) from male Wistar rats were aerobically (37 degrees C) perfused (20 min) with bicarbonate buffer. This was followed by a 3-min infusion of St. Thomas' Hospital cardioplegic solution containing various concentrations of CoQ10 (0, 1, 3, 6, 12, and 58 mumol/L). Hearts were then subjected to 180 min of hypothermic (20 degrees C) global ischemia and 35 min of normothermic (37 degrees C) reperfusion (15 min Langendorff, 20 min working). Ventricular fibrillation (Vf) upon reperfusion was irreversible in the 12 and 58 mumol/ L CoQ10 groups (4/6 and 3/6, respectively). In the hearts which Vf upon reperfusion was not irreversible, the percent recovery of aortic flow (%AF) was 43.3 +/- 5.4% (n = 9) in the control group versus 31.6 +/- 7.7% (n = 6), 38.0 +/- 12.0% (n = 6), 27.2 +/- 6.9% (n = 6), 31.3% (n = 2), and 30.4 +/- 14.2% (n = 3) in the 1, 3, 6, 12, and 58 mumol/L CoQ10 groups, respectively. Creatine kinase leakage during Langendorff reperfusion tended to be greater in the 12 and 58 mumol/L CoQ10 groups than in the control group. Thus, CoQ10 in the cold cristalloid cardioplegic solution induced irreversible Vf upon reperfusion and failed to improve functional recoveries following hypothermic global ischemia.
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PMID:[The effect of coenzyme Q10 and cold cristalloid cardioplegia on hypothermic global ischemia]. 896 87

The aim of this study was to relate changes in the redox state of mitocondrial electron carriers to the 'burst' of oxyradicals in postischemic myocardium. The free radical EPR signals of control and re-oxygenated rat hearts were mainly due to coenzyme Q10, the line width was 0.81 +/- 0.02 mT, and the intensities (1.58 +/- 0.12) x 10(16) and (1.41 +/- 0.13) x 10(16) spins/g. The low-temperature spectra of oxygenated myocardium contained a predominant signal from a S3 Fe-S center and weak signals from N1b, N2, N3, N4 and S1 centers. Global ischemia caused cardinal changes in the redox state of the mitochondrial respiratory chain. The low-temperature EPR spectrum now contained intensive signals from most Fe-S centers. The amount of coenzyme Q10 semiquinones decreased during global ischemia, but the content of flavosemiquinones increased. The line width of the signal of the ischemic heart was 1.28 +/- 0.03 mT, and its intensity corresponded (3.16 +/- 0.94) x 10(16) spins/g. The spin-trapping experiments with TEMPONE-H showed that the rate of oxyradical generation in isolated cardiomyocytes essentially increased after hypoxia or on adding rotenone and antimycin A. It became equal to 4.2 +/- 0.3, 8.2 +/- 0.6 and 7.1 +/- 0.5 nmol/min mg-1 mitochondrial protein, respectively. The maximal stimulatory effect was observed in the presence of both inhibitors. The addition of superoxide dismutase, but not catalase, suppressed the formation of oxyradicals.
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PMID:The redox state of coenzyme Q10 in mitochondrial respiratory chain and oxygen-derived free radical generation in cardiac cells. 926 5

It has been hypothesized that CoQ10 (CoQ) pretreatment protects myocardium from ischemia reperfusion (I/R) injury by its ability to increase aerobic energy production as well as its activity as an antioxidant. Isolated hearts from rats pretreated with either CoQ 20 mg/kg i.m. and 10 mg/kg i.p. or vehicle 24 and 2 h prior to the experiment, were subjected to 15 min of equilibration (EQ), 25 min of ischemia, and 40 min of reperfusion (RP). Developed pressure, +/-dp/dt, myocardial oxygen consumption, and myocardial aerobic efficiency (DP/MVO2) were measured. 31P NMR spectroscopy was used to determine ATP and PCr concentrations. Lucigenin-enhanced chemiluminescence of the coronary sinus effluent was utilized to determine oxidative stress through the protocol. CoQ pretreatment improved myocardial function after ischemia reperfusion. CoQ pretreatment improved tolerance to myocardial ischemia reperfusion injury by its ability to increase aerobic energy production, and by preserving myocardial aerobic efficiency during reperfusion. Furthermore, the oxidative burst during RP was diminished with CoQ. Similarly it was hypothesized that CoQ protected coronary vascular reactivity after I/R via an antioxidant mechanism. Utilizing a newly developed lyposomal CoQ preparation given i.v. 15 min prior to ischemia, ischemia reperfusion was carried out on Langendorff apparatus as previously described. Just prior to ischemia and after RP, hearts were challenged with bradykinin (BK) and sodium nitroprusside (SNP) and change in coronary flow was measured. CoQ pretreatment protected endothelial-dependent and endothelial-independent vasodilation after I/R. We conclude that CoQ pretreatment protects coronary vascular reactivity after I/R via OH radical scavenger action.
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PMID:The mechanisms of coenzyme Q10 as therapy for myocardial ischemia reperfusion injury. 926 22


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