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

Oxygen-derived free radicals have been implicated in causing degradation of myocardial membrane phospholipids associated with ischemia and reperfusion. Since iron is known to catalyze the hydroxyl radical formation responsible for cellular injury, this study was designed to relate the role of iron with phospholipid breakdown in ischemic-reperfused heart. Isolated rat heart perfused by the Langendorff technique was subjected to 30 min of normothermic ischemia followed by 30 min of reperfusion. The experimental group received 0.6 mM deferoxamine, an iron chelator, before reperfusion of ischemic myocardium. Deacylation and reacylation of membrane phospholipids were monitored by using [14C]arachidonic acid (AA), whereas the de novo phospholipid synthesis was evaluated by using [3H]glycerol in the perfusate. In the deferoxamine group, the loss of [14C]phosphatidylcholine (PC) and the corresponding accumulation of isotopic lysophosphoglycerides as well as AA was significantly lower compared with the control. The incorporation of radioactivity for [14C]AA and [3H]glycerol into phospholipids was significantly increased in the treated group compared with the untreated group. In addition, decreased malonaldehyde formation and lactate dehydrogenase release, a higher recovery of high-energy phosphate compounds, and myocardial contractility were noticed in the deferoxamine-treated hearts. These results indicated that postischemic administration of an iron chelator such as deferoxamine can preserve membrane phospholipids and reduce myocardial dysfunction associated with reperfusion of ischemic heart.
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PMID:Role of iron on membrane phospholipid breakdown in ischemic-reperfused rat heart. 222 Nov 18

Fourteen randomized patients undergoing myocardial revascularization were divided into group A standard hypothermic cardioplegic solution) and group B (the same cardioplegic solution supplemented with deferoxamine 1000 mg/L). In all patients myocardial biopsy specimens were obtained before ischemia and during reperfusion and were assessed for chemiluminescence (to indirectly determine oxygen-free radical activity) and for electron microscopic studies. Chemiluminescence in group A showed a photoemission of 36.5 +/- 1.5 cpm/mg protein X10(-3) for the preischemia samples and 72 +/- 5.7 cpm/mg protein X10(-3) for the reperfusion samples (p less than 0.01). In the patients who received deferoxime (group B), values for chemiluminescence for preischemia and reperfusion samples were not significantly different. Electron microscopic studies showed a significant increase in grade 4 (severely damaged) mitochondria in reperfusion biopsy specimens from both groups as compared with preischemia samples. However, reperfusion samples from group B showed a better preservation of myocardial cells with marked reduction of grade 4 (severely damaged) mitochondria. These results support the hypothesis that oxygen-free radicals are responsible in part for the production of reperfusion injury in the human heart. They suggest that this mechanism may be at least partially controlled by adding an iron chelating agent such as deferoxime.
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PMID:Effect of supplementing cardioplegic solution with deferoxamine on reperfused human myocardium. 223 33

U78517F is a novel inhibitor of iron-catalyzed lipid peroxidation that combines the tetramethylchroman antioxidant ring portion of alpha-tocopherol with the amine of the previously described 21-aminosteroids (e.g., U74006F). U78517F inhibited 200 microM FeCl2-initiated lipid peroxidation in rat brain homogenates by 50% at a concentration of 0.6 microM compared with 8 microM for U74006F, 28 microM for alpha-tocopherol, and 43 microM for the ring portion of alpha-tocopherol (i.e., trolox). U78517F is devoid of hypothermic or antiexcitotoxic actions or interactions with known neurotransmitter receptors. When administered intraperitoneally to male gerbils at 10 minutes before and again at the end of a 3-hour period of unilateral carotid artery occlusion, U78517F decreased 24-hour postischemic cortical neuronal necrosis. Neuronal density in the medial portion of the cortex was increased from 34.2% of normal in vehicle-treated animals to 86.3% in the U78517F-treated animals. In the lateral cortical area, the vehicle group showed only 3.3% neuronal survival versus 48.2% in the drug-treated group. In a separate series of experiments with the same focal ischemia model, identical dosing with U78517F enhanced the postischemic recovery of cortical extracellular calcium without any effect on ischemic or postischemic cortical blood flow. The effect on calcium recovery was observed at intraperitoneal doses as low as 0.1 mg/kg. The compound also was effective in partially attenuating 1-week postischemic hippocampal CA1 neuronal loss in a gerbil global ischemia model involving brief (15-minute) bilateral carotid occlusion, but sustained dosing was required. These results document the anti-ischemic efficacy of a novel and potent inhibitor of iron-catalyzed lipid peroxidation and further support a key role of oxygen radicals in postischemic brain damage.
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PMID:Nonsteroidal lazaroid U78517F in models of focal and global ischemia. 223 90

Cardiac mitochondrial function as measured by oxidative phosphorylation is impaired by ischemia; and, this deteriorates even further on reperfusion of the heart. Free oxygen radicals, especially the formation of hydroxyl radicals via the iron-catalyzed Haber-Weiss and Fenton reactions have been implicated in the reperfusion injury. In this study, the effect of desferrioxamine (desferal) in the perfusate on mitochondrial function of isolated rat hearts during different periods of normothermic ischemic cardiac arrest (NICA), and subsequent reperfusion was investigated. Mitochondrial functions measured were the QO2 (state 3); ADP/O ratio and oxidative phosphorylation; the mitochondrial, loosely bound (chelateable) iron (LB-iron); the xanthine dehydrogenase and xanthine oxidase activities. Inclusion of desferal in the perfusion solution significantly improved mitochondrial function during the different NICA periods, and prevented the deterioration of mitochondrial function resulting from reperfusion. Desferal did not significantly affect the LB-iron content of the mitochondria or the ratio of xanthine dehydrogenase/xanthine oxidase activities in the mitochondria during NICA or reperfusion. Our experiments suggest that iron, which is free to be chelated by desferal, plays a role in this injury to the rat myocardium.
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PMID:The effect of desferal on rat heart mitochondrial function, iron content, and xanthine dehydrogenase/oxidase conversion during ischemia-reperfusion. 228 9

Disorders of hemoglobin synthesis affect the musculoskeletal system by either causing replacement of bone by hematopoietic tissue, precipitating bone and soft tissue ischemia and necrosis, or a combination of both processes. Less frequently, joints are involved by synovial ischemia, synovial deposition of iron, or microfracture of subchondral bone. Osteopenia is a significant problem in both thalassemia and sickle cell anemia and may result in vertebral and long bone fractures. Growth disturbances are frequently seen but are not often appreciated until adolescence because of improved hematologic management. The cause of the growth problems is multifactorial and may be related to hormonal deficiencies, iron overload, hypoxia, or local trauma to the growth plate secondary to significant osteopenia.
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PMID:Musculoskeletal problems in hemoglobinopathy. 229 57

We have developed a method to quantify and map regional wall thickening throughout the left ventricle (LV) with magnetic resonance imaging. In contrast to methods that measure planar wall thickness and thickening, this method uses the three-dimensional (3D) geometry of the left ventricle to calculate the perpendicular thickness of the wall. We tested this method at three levels of increasing complexity using 1) phantom studies, 2) in vivo experiments in dogs with normal cardiac function, and 3) in vivo studies in dogs during acute ischemia. Experiments were conducted in 15 open-chest dogs imaged by a 0.38 T iron core magnet. Five short-axis images at end diastole and end systole were obtained with the spin echo technique by use of the QRS as a trigger for end diastole and the second heart sound, S2, to time end systole. After acquisition of preischemic images, acute ischemia was induced by either coronary artery ligation (n = 5) or intracoronary dental rubber injection (n = 5), which produced severe transmural ischemia. By use of computer-aided contouring of the endocardial and epicardial borders, each image was divided into 16 segments with radial lines originating from the midwall centroid. A 3D volume element was defined as that generated by connecting two matched planar segments in two adjacent image planes. This defined 64 volume elements comprising the entire left ventricle. Thickness and thickening before and during ischemia were then calculated by using the planar segments and the 3D volume elements. In phantom studies, the 3D method was accurate, independent of the angle of inclination of the image plane to the phantom wall, whereas the planar method showed considerable overestimation of thickness when the image plane was oblique to the phantom wall. In the dogs before induction of ischemia, the 3D method demonstrated the well-established normal taper in end-diastolic wall thickness from 1.10 +/- 0.02 cm at the base to 1.05 +/- 0.11 cm at the apex (p less than 0.01). By contrast, the planar method did not detect the decrease in thickness toward the apex (1.13 +/- 0.07 cm at the base vs. 1.16 +/- 0.14 cm at the apex, p = NS). During acute ischemia, thickening was calculated by both methods at the center of the ischemic zone defined by Monastral blue nonstaining and compared with the preischemic values.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Quantification and validation of left ventricular wall thickening by a three-dimensional volume element magnetic resonance imaging approach. 229 33

Since hydrogen peroxide (H2O2) can react with ferrous iron (FE++) to form the more toxic hydroxyl radical (OH) in vitro, and since H2O2 is generated brain xanthine oxidase (XO) during ischemia/reperfusion (I/R), we hypothesized that gerbils depleted of iron by dietary restriction or treated with iron chelators would be less susceptible to I/R injury. We found that gerbils fed a low iron diet for 8 weeks had decreased brain and serum iron levels, less neurologic deficits, and decreased brain edema after temporary unilateral carotid ligation (ischemia) and then reperfusion than gerbils fed a control standard iron diet. In addition, brains from gerbils treated with iron-free deferoxamine (an iron chelator), but not iron-loaded deferoxamine, had decreased (P less than .05) brain edema following ischemia and reperfusion. The results indicate that iron may contribute to cerebral ischemia/reperfusion damage.
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PMID:Iron depletion or chelation reduces ischemia/reperfusion-induced edema in gerbil brains. 230 92

Contractile dysfunction of viable, previously ischemic stunned myocardium is thought to be due to reactive oxygen species generated during ischemia/reperfusion. Direct in vivo evidence that oxidants cause systolic or diastolic dysfunction of viable myocardium has, however, been lacking. We sought to determine whether in vivo exposure of canine myocardium to exogenously generated reactive oxygen species could--in the absence of myocardial ischemia or necrosis--"mimic" the depressed systolic contractile function, paradoxical contraction during early diastole, and prolonged diastolic relaxation time characteristic of stunned myocardium. Anesthetized open-chest dogs were randomly assigned to receive either (1) the free radical generating substrates xanthine oxidase + purine + iron-saturated transferrin or (2) saline, infused directly into an anterior coronary vein. Infusion of free radical substrates did not cause ischemia: regional myocardial blood flow and myocardial high-energy phosphate stores were normal in both groups. Furthermore, infusion of xanthine oxidase + purine + transferrin was not associated with histologic or electron microscopic evidence of myocyte injury or death in this model. Xanthine oxidase + purine + transferrin did, however, produce marked abnormalities in regional systolic contractile function; at 2 hours after the onset of infusion, segment shortening (assessed by sonomicrometry) in the perfused region of the heart averaged 62 +/- 5% of baseline, preinfusion values in animals infused with free radical substrates versus 113 +/- 8% of baseline values in saline-administered control dogs (p less than 0.004). This systolic dysfunction was effectively reversed by administration of the free radical scavenging agents superoxide dismutase + catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo infusion of oxygen free radical substrates causes myocardial systolic, but not diastolic dysfunction. 232 2

Considerable evidence suggests that free radicals engendered by redox-active metals, particularly iron and copper, are causative agents in reperfusion injury following ischemia. This study demonstrates that perfusion of the isolated rat heart with a buffer containing zinc, a non-redox active metal similar to copper in its coordination chemistry, inhibits the development of ventricular arrhythmias during reperfusion. Zinc was employed as the bishistidine complex, Zn--His2, to maintain solubility and permeability. Zn--His2 exerted an antiarrhythmic activity as hearts spent a longer time in normal sinus rhythm and a shorter time in ventricular fibrillation during reperfusion following 10 min of regional ischemia. However, Zn--His2 also produced a negative inotropic and chronotropic effect, evident during equilibration and ischemia. In the course of experiments which began in Israel and continued in the U.S. it was necessary to use two different sources of rats. Hearts from the two sources manifested different sensitivities to the concentrations of Zn--His2, although their physiological effects were similar. Differential activity responses were noted for antiarrhythmic activity, negative inotropic and chronotropic properties, and toxicity. In both groups of untreated hearts the incidence of ventricular fibrillation after ischemia was 100%. Ventricular fibrillation was reduced to 17% at 37.5 microM Zn--His2 in the U.S.-bred rat hearts and to 9% at 200 microM Zn--His2 in those from Israel. These changes in Zn--His2 treated animals were accompanied by a decrease in lactate dehydrogenase release from the myocardium during reperfusion. None of the protective effects was due to histidine alone. These results indicate that zinc prevents ventricular arrhythmias during reperfusion following regional ischemia and may prevent membrane damage, possibly, by reduction of free radical formation.
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PMID:The effect of zinc on reperfusion arrhythmias in the isolated perfused rat heart. 232 82

We have applied a superparamagnetic iron oxide formulation (AMI-25, Advanced Magnetics, Inc., Cambridge, MA) to image the cerebral vasculature. Contrast-enhanced images of normal anesthetized rats demonstrated excellent gray/white matter differentiation, consistent with known differences in blood perfusion, and cerebrospinal fluid spaces were clearly seen. Alterations in normal perfusion patterns due to barbiturate anesthesia and ischemia were clearly visible. We propose the use of this agent as an adjunct to MRI for the imaging of conditions with perfusion abnormalities.
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PMID:Assessment of a superparamagnetic iron oxide (AMI-25) as a brain contrast agent. 232 43


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