Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

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

The aim of the work was to evaluate the effect of CoQ10 (10 mg/kg body weight) on the morphological changes in the rat brain after the Et-1 induced cerebral ischemia. Selective necrotic foci and dark neurons were observed in the cerebral cortex, hippocampal CA1, CA2 sectors and dentate gyrus after the administration of Et-1. Around the necrotic foci, glycogen was deposited 24 hours after the ischemic hypoxia. It seems that histopathological changes evoked by Et-1 indicate the complicated mechanism connected with ischemia. After treatment with CoQ10 only sparse neuronal changes were observed. CoQ10, known oxygen-derived free radicals scavenger diminished neuronal damage in the cerebral cortex and in the hippocampus.
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PMID:Evaluation of morphological changes after treatment with coenzyme Q10 (CoQ10) in endothelin-1 induced experimental ischemia in the rat. 983 95

The inferior recovery of cardiac function after interventional cardiac procedures in elderly patients compared to younger patients suggests that the aged myocardium is more sensitive to stress. We report two studies that demonstrate an age-related deficit in myocardial performance after aerobic and ischemic stress and the capacity of CoQ10 treatment to correct age-specific diminished recovery of function. In Study 1 the functional recovery of young (4 mo) and senescent (35 mo) isolated working rat hearts after aerobic stress produced by rapid electrical pacing was examined. After pacing, the senescent hearts, compared to young, showed reduced recovery of pre-stress work performance. CoQ10 pretreatment (daily intraperitoneal injections of 4 mg/kg CoQ10 for 6 weeks) in senescent hearts improved their recovery to match that of young hearts. Study 2 tested whether the capacity of human atrial trabeculae (obtained during surgery) to recover contractile function, following ischemic stress in vitro (60 min), is decreased with age and whether this decrease can be reversed by CoQ10. Trabeculae from older individuals (> or = 70 yr) showed reduced recovery of developed force after simulated ischemia compared to younger counterparts (< 70 yr). Notably, this age-associated effect was prevented in trabeculae pretreated in vitro (30 min at 24 degrees C) with CoQ10 (400 MicroM). We measured significantly lower CoQ10 content in trabeculae from > or = 70 yr patients. In vitro pretreatment raised trabecular CoQ10 content to similar levels in all groups. We conclude that, compared to younger counterparts, the senescent myocardium of rats and humans has a reduced capacity to tolerate ischemic or aerobic stress and recover pre-stress contractile performance, however, this reduction is attenuated by CoQ10 pretreatment.
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PMID:Coenzyme Q10 improves the tolerance of the senescent myocardium to aerobic and ischemic stress: studies in rats and in human atrial tissue. 1041 43

The antioxidant and bioenergetic effects of CoQ10 are well known but its clinical utility is limited by the requirement for enteral administration. A newly developed liposomal CoQ10 (CoQ) is water soluble and capable of intravenous administration. The purpose of this study is to determine the mechanism by which acute administration CoQ protects myocardium from reperfusion (Rp) injury. Rats were pretreated with CoQ 10 mg/kg i.v. 30 min prior to the experiment. Control rats were pretreated with liposome only. Hearts were excised and subjected to equilibration, 25 min of normothermic ischemia and 40 min of Rp on a Langendorff apparatus. At end Rp, CoQ hearts recovered 74 +/- 5% of their DP vs. 50 +/- 9% in control (p < 0.05). Aerobic efficiency was maintained (0.66 +/- 0.02 vs. control, 0.5 +/- 0.04, p < 0.003) and CoQ hearts lost less CK activity vs. control (p < 0.02). PCr and ATP were higher than control (p < 0.05, 0.02, respectively). Results show that i.v. CoQ improves recovery of function, aerobic efficiency, CK activity, and recovery of PCr and ATP after Rp. This suggests that acute administration of liposomal CoQ improves myocardial tolerance to I/R via its role as an antioxidant as well as improving oxygen utilization and high energy phosphate production.
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PMID:Bioenergetic effect of liposomal coenzyme Q10 on myocardial ischemia reperfusion injury. 1041 45

In a surgical model of liver ischemia lipid peroxidation occurs, as shown by increase of lipid peroxidation end products, endogenous CoQ9 is oxidized and mitochondrial respiration is lowered; however, pre-treatment of the rats by i.p. injection of CoQ10 for 14 days normalizes the above parameters, presumably by way of the observed high extent of reduction of the incorporated quinone; moreover, liver homogenates of the CoQ10-treated rats are more resistant than those of non-treated rats to oxidative stress induced by an azido free radical initiator. This preliminary study suggests that CoQ10 pre-treatment can be of beneficial effect against oxidative damage during liver surgery transplantation.
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PMID:Protective effect of exogenous coenzyme Q in rats subjected to partial hepatic ischemia and reperfusion. 1041 51

Male Wistar rats were subjected to intraperitoneal (i.p.) streptozotocin (STZ) administration (85 mg/kg) to evoke diabetes. Cerebral ischaemia was produced by injection of 0.03 ml of air into the left carotid followed by bilateral common carotid ligation. We studied the effect of application of two antioxidants--coenzyme Q10 (CoQ10, 10 mg/kg b.w., i.p. for seven days) and lipoic acid (LA, 100 mg/kg b.w., i.p. for seven days) on neurones and on the apoptosis-related enzyme--caspase-3 activity in the hippocampus and dentate gyrus. Ischaemia and diabetes lead to a decrease of nuclear and perikaryon diameters as well as neuronal density in the CA1, CA2, CA3 and dentate gyrus. Application of CoQ10 or LA for seven days improved the mean nucleus area and perikaryon area in almost all investigated structures. Both antioxidants diminished neuronal loss in the diabetes complicated with ischaemia but not in the animals with diabetes only. Activity of one of the key enzymes in apoptotic cell death, caspase-3 (CPP32), increased in hippocampus in the diabetic rats, in the animals with cerebral ischaemia and in the rats with both diabetes and ischaemia by about 80%, 33% and 53%, respectively. Either the CoQ10 or the LA treatment led to a significant decrease of the CPP32 activity in all experimental groups. Our results confirm the presence of neuronal damage and death in the hippocampus and dentate gyrus in the experimental STZ-diabetes and its aggravation by the additional cerebral ischaemia. The effects of the antioxidative treatment support the hypothesis of an important role of oxidative stress and free radicals in neuronal pathology in diabetes and ischaemia. The above results of CPP32 activity suggest an important role of apoptosis as a mechanism of cell death and demonstrate the positive effect of the CoQ10 and the LA treatment.
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PMID:Neuronal death in the rat hippocampus in experimental diabetes and cerebral ischaemia treated with antioxidants. 1177 Jan 25

We have derivatised alpha-tocopherol (vitamin E) to a water-soluble polyoxyethanyl-alpha - tocopheryl sebacate (PTS) and discovered that it formed a non-covalent complex with CoQ10 at a molar ratio of 2:1 (PTS-CoQ10). This complex was water-soluble and remained stable for extended periods of time. After oral delivery of the formulation into rats PTS was hydrolysed to vitamin E and elevated levels of both vitamin E and CoQ10 in blood plasma were detected within 1 h. Thus, this aqueous formulation contains a combination of two potent antioxidants. The formulation's efficacy was tested against ischemic brain damage caused by a transient (8 min) bilateral occlusion of the common carotid arteries in rats. The animals received PTS-CoQ10 by two intraperitoneal injections given immediately after ischemia and 3 h later and the brain damage was assessed up to 12 days post-ischemia. A significant neuroprotection was observed in the CA1 hippocampal region, for example at 12 days approximately 50% of CA1 neurons were still alive in the treated animals versus less than 5% in the non-treated group. Our data is consistent with previously published observations indicating the therapeutic potential of antioxidants for treatments of ischemia/reperfusion injuries and the formulation described here is particularly appropriate for the application in acute conditions, such as stroke or cardiac arrest.
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PMID:Derivatised alpha-tocopherol as a CoQ10 carrier in a novel water-soluble formulation. 1469 33


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