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

The role of superoxide radical formation in the pathogenesis of perinatal hypoxic-ischemic injury was examined using transgenic (Tg) mice expressing three times normal amounts of copper/zinc-superoxide dismutase (CuZn/SOD). Fourteen litters of postnatal d 7 strain 218/3 mice were subjected to right common carotid artery ligation followed by 90 min of hypoxia in an 8% oxygen/humidified chamber maintained at 37 degrees C. Both Tg mice (n = 32) and their nontransgenic (nTg) littermates (n = 30) survived the injury equally. Evaluation of infarcted brain areas measured by video image analysis of three coronal brain sections through the anterior hippocampus from each animal revealed that the Tg animals suffered brain infarction more frequently than did nTg mice. Blinded histologic scoring of cerebral cortex and striatum 5 d after injury revealed that Tg mice were more likely to have higher histologic severity scores than their nTg littermates (p = 0.0463, Mann-Whitney U test). These findings suggest that brain injury in perinatal hypoxia-ischemia may be mediated in part by free radical formation from excessive hydrogen peroxide or nitric oxide production.
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PMID:Brain injury after perinatal hypoxia-ischemia is exacerbated in copper/zinc superoxide dismutase transgenic mice. 882 88

A two turn saddle shaped surface coil receiver was developed that allowed high resolution magnetic resonance imaging of the rat spinal cord. This is particularly important in laboratory animals where central nervous system regions of interest are relatively small. A continuous copper wire 1.5 mm in diameter was wound into two turns 28 mm in diameter. The saddle shape of the second turn improved the homogeneity of the signal within the region of interest and maintained sufficient field of view and depth of penetration. The quality factor (Q) for the surface coil was Q = 199 unloaded, and Q = 60 loaded. Using this surface coil with a GE CSI II 2.0 Tesla small bore magnet, spin echo T1 (TR = 500 msec, TE = 25 msec) and T2 (TR = 2000 msec, TE = 100 msec) weighted images were obtained in cross section, using 2 mm slice thickness with 2 excitations per phase encoding step. A sagittal gradient echo (rapid scan, TR = 85 msec, TE = 10 msec) was used to document reestablishment of vascular flow following ischemia. Spinal cord ischemia was induced by 14 minute temporary occlusion of spinal cord blood supply. MRI was performed at 18 hours following ischemia. There was a 1.4 fold increase in T2 image intensity in ischemic rat spinal cord (n = 4), consistent with edema formation, compared to normal rat spinal cord (n = 4). Preliminary studies show that similar high resolution images can be performed on the rat brain. This technique uses standard MRI equipment and the surface coil is made from inexpensive readily available materials. There are various animal models of cerebral and spinal cord injury that would benefit from improved high resolution MRI. This coil design may have application in larger animal models and the clinical setting.
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PMID:High resolution magnetic resonance imaging of the rat spinal cord. 891 65

The objective of this study was to determine whether ischemia and reperfusion (I/R) and/or chronic arterial hypertension potentiates the leukocyte-endothelial cell adhesion (LECA) and microvascular dysfunction elicited by oxidized low-density lipoproteins (ox-LDL). Mast cell degranulation, leukocyte adherence and emigration, and albumin leakage were monitored in postcapillary venules of rat mesentery. Intra-arterial infusion of copper-oxidized LDL (Cu-LDL), at a concentration that does not directly affect the microvasculature, significantly enhanced the I/R-induced recruitment of adherent and emigrated leukocytes but does not affect the increased albumin leakage and mast cell degranulation responses normally observed after I/R. Infusion of a higher concentration of Cu-LDL in nonischemic mesentery of either normotensive Wistar-Kyoto or spontaneously hypertensive rats elicited significant yet similar increases in LECA, mast cell degranulation, and albumin leakage. These findings indicate that 1) ox-LDL act synergistically with I/R to promote leukocyte recruitment in postcapillary venules but without an accompanying exacerbation of albumin leakage, and 2) ox-LDL do not elicit a more intense inflammatory response in the microvasculature of hypertensive versus normotensive animals.
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PMID:Oxidized low-density lipoproteins and microvascular responses to ischemia-reperfusion. 899 11

An isolated rabbit heart Langendorff preparation paced electrically was used to evaluate the effects of a highly purified, high molecular weight fraction of oligomeric procyanidines isolated from Vitis vinifera seeds on myocardial reperfusion injury after 40 minutes of low flow (1 ml/min) ischemia. Infusion of the heart with 100 or 200 micrograms/ml procyanidines dose-dependently reduced ventricular contracture during ischemia (LVEDP values decreased by 28% and 51%), decreased coronary perfusion pressure (CPP), improved cardiac mechanical performance upon reperfusion, increased the release of 6-keto-PGF1 alpha into the perfusate in both the pre-ischemic and the reperfusion periods (by 68% at 200 micrograms/ml), and suppressed rhythm irregularity. This antiarrhythmogenic action was confirmed in a more severe model of ischemia (flow rate 0.2 ml/ min). The cardioprotective agent allopurinol infused at 20 micrograms/ml had effects on the contractility and on the release of 6-keto-PGF1 alpha comparable to those of 200 micrograms/ml procyanidines. The results of the second part of this study show that procyanidines are potent scavengers of several reactive oxygen species involved in the ischemia/reperfusion damage: the superoxide anion (IC50 = 5.64 microM: rate constant K = 7.55 x 10(5) M-1 s-1, determined by the phenazine methosulfate/NADH method); the hydroxyl radical (IC50 = 28 microM; rate constant K = 1.2 x 10(12) M-1 s-1, determined by the electron spin resonance spectroscopy); peroxyl radicals (IC50 = 0.025 microM and 0.35 microM, determined using two different lipid substrates, phosphatidylcholine liposomes and methyl linoleate micelles by UV spectroscopy at 233 nm). Finally, procyanidines interact with Fe2+ and Cu2+ ions (the catalysts of HO. radicals production) giving rise to strong complexes, with stability constants (log K) ranging from 9.35 to approximately 9.
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PMID:Procyanidines from Vitis vinifera seeds protect rabbit heart from ischemia/reperfusion injury: antioxidant intervention and/or iron and copper sequestering ability. 900 Aug 80

In a number of interventions, it is desirable to be able to produce a rapid but readily reversible change in spinal cord temperature (SCT) without altering general body temperature and to maintain this selective spinal cord hypothermia stable for an extended interval. To accomplish this, we developed a technique of subcutaneous perfusion cooling in rat. This was accomplished by constructing a copper heat exchanger which was readily implanted into subcutaneous space overlying the upper thoracic to upper sacral spinal segments. The heat exchanger was then perfused with fluid from an external temperature bath maintained at (8 degrees C) at a perfusion rate of 100 ml/min. The temperature of the heat exchanger was controlled by regulating the pump with a feed back controller driven by a thermocouple placed percutaneously into the paraspinal musculature. A series of studies were performed to demonstrate the characteristics and utility of this cooling technique. Lowering the pump set point to 24 degrees C resulted in a fall in the intrathecal temperature (ITT) to 27 +/- 0.3 degrees C within 15 min with no significant changes observed in rectal temperature (37.5- > 37.2 degrees C). Change in intrathecal temperature showed a highly significant correlation with changes in paravertebral muscle temperature (r = 0.977). The hypothermic state could be readily maintained for extended intervals up to 5 h and an underbody heating pad was used to maintain rectal temperature between 35-36.5 degrees C. Lowering the ITT from 37 degrees C-27 degrees C evoked a temperature-dependent increase in the latency of precooling spinal somatosensory evoked potentials (SSEPs) with the highest sensitivity observed in postsynaptic components. Returning the set point temperature back to 37 degrees C produced a rapid recovery of the SSEPs latencies. Consistent with previously published data, selective spinal cord hypothermia (27 degrees C) provided complete protection against otherwise injurious interval of normothermic ischemia produced by balloon occlusion of the descending aorta. This technique provides a simple, relatively non-invasive and reliable experimental tool for studying the effect of selective, acute and/or prolonged spinal cord hypothermia.
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PMID:Technique of selective spinal cord cooling in rat: methodology and application. 921 May 79

Direct evidence for substantial iron and copper mobilization into the coronary flow immediately following prolonged, but not short, cardiac ischemia is presented. When small volumes of coronary flow fractions (CFFs) were serially collected upon reperfusion, after 25-60 min of ischemia, the copper and iron levels in the first CFF were 50-fold and 12- to 15-fold higher, respectively, than corresponding pre-ischemic values. The copper and iron levels after shorter periods (15-21 min) of ischemia were only about five-fold higher than the pre-ischemic values. This demonstrates that the resumption of coronary flow is accompanied by a burst of both metal ions. The levels of Cu/Fe in the CFFs correlated well with the loss of cardiac function following global ischemia of varying duration. After 18 min of ischemia, the residual cardiac function was less than 50%, and the damage was essentially reversible. After 25 min of ischemia, it exceeded 50% and was only partially reversible, while after 35 min, the damage exceeded 80%, and was mostly irreversible. The results are in accord with the hypothesis that copper and iron play causative roles in myocardial injury through mediation of hydroxyl radical production. Thus, the pattern of Cu/Fe mobilization from the tissue into the CFF can be used for the prediction of the severity of myocardial damage following ischemia, and could be developed into useful modalities for intervention in tissue injury.
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PMID:Patterns of mobilization of copper and iron following myocardial ischemia: possible predictive criteria for tissue injury. 940 77

The effects of Cu(II) and the stable nitroxide radical 4-OH-2, 2, 6, 6-tetramethyl-piperidine-1-oxyl (TPL) on reperfusion injury following global myocardial ischemia have been studied using the isolated rat heart model in the Langendorff configuration. Hearts were equilibrated with Krebs-Henseleit buffer (KH-buffer) for 10 min and subjected to 18 min of normothermic global ischemia. After 20 min reperfusion, hemodynamic parameters recovered as follows: ventricular developed pressure (77%), dP/dt (71%) and -dP/dt (80%), heart rate (91%), and work index (70%). End-diastolic pressure was 16 mm Hg. When 10 microM Cu-nitrilotriacetate or Cu-(histidine)2 was included in the perfusate before, during, and following ischemia, the heart injury was more extensive and the work index only recovered to 17% of the preischemic value. The inclusion of 100 microM TPL during reperfusion abolished the copper-induced sensitization. In the absence of copper, TPL did not provide any protection against ischemia-reperfusion damage to the heart. The inclusion of 100 microM 1,4-dihydroxy-2,2,6,6-tetramethylpiperidine (TPL-H) during reperfusion, partially abolished the copper-induced sensitization. Since conversion between TPL and TPL-H takes place, the fact that both forms provide protection can increase their protective efficacy.
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PMID:Nitroxide radicals prevent metal-aggravated reperfusion injury in isolated rat heart. 945 98

The middle domain of plasma histidine-proline-rich glycoprotein (HPRG) contains unusual tandem pentapeptide repeats (consensus G(H/P)(H/P)PH) and binds heparin and transition metals. Unlike other proteins that interact with heparin via lysine or arginine residues, HPRG relies exclusively on histidine residues for this interaction. To assess the consequences of this unusual requirement, we have studied the interaction between human plasma HPRG and immobilized glycosaminoglycans (GAGs) using resonant mirror biosensor techniques. HPRG binding to immobilized heparin was strikingly pH-sensitive, producing a titration curve with a midpoint at pH 6.8. There was little binding of HPRG to heparin at physiological pH in the absence of metals, but the interaction was promoted by nanomolar concentrations of free zinc and copper, and its pH dependence was shifted toward alkaline pH by zinc. The affinity of HPRG for various GAGs measured in a competition assay decreased in the following order: heparin > dermatan sulfate > heparan sulfate > chondroitin sulfate A. Binding of HPRG to immobilized dermatan sulfate had a midpoint at pH 6.5, was less influenced by zinc, and exhibited cooperativity. Importantly, plasminogen interacted specifically with GAG-bound HPRG. We propose that HPRG is a physiological pH sensor, interacting with negatively charged GAGs on cell surfaces only when it acquires a net positive charge by protonation and/or metal binding. This provides a mechanism to regulate the function of HPRG (the local pH) and rationalizes the role of its unique, conserved histidine-proline-rich domain. Thus, under conditions of local acidosis (e.g. ischemia or hypoxia), HPRG can co-immobilize plasminogen at the cell surface as well as compete for heparin with other proteins such as antithrombin.
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PMID:Histidine-proline-rich glycoprotein as a plasma pH sensor. Modulation of its interaction with glycosaminoglycans by ph and metals. 948 72

Superoxide and superoxide-derived oxidants have been hypothesized to be important mediators of postischemic injury. Whereas copper, zinc-superoxide dismutase, SOD1, efficiently dismutates superoxide, there has been controversy regarding whether increasing intracellular SOD1 expression would protect against or potentiate cellular injury. To determine whether increased SOD1 protects the heart from ischemia and reperfusion, studies were performed in a newly developed transgenic mouse model in which direct measurement of superoxide, contractile function, bioenergetics, and cell death could be performed. Transgenic mice with overexpression of human SOD1 were studied along with matched nontransgenic controls. Immunoblotting and immunohistology demonstrated that total SOD1 expression was increased 10-fold in hearts from transgenic mice compared with nontransgenic controls, with increased expression in both myocytes and endothelial cells. In nontransgenic hearts following 30 min of global ischemia a reperfusion-associated burst of superoxide generation was demonstrated by electron paramagnetic resonance spin trapping. However, in the transgenic hearts with overexpression of SOD1 the burst of superoxide generation was almost totally quenched, and this was accompanied by a 2-fold increase in the recovery of contractile function, a 2.2-fold decrease in infarct size, and a greatly improved recovery of high energy phosphates compared with that in nontransgenic controls. These results demonstrate that superoxide is an important mediator of postischemic injury and that increasing intracellular SOD1 dramatically protects the heart from this injury. Thus, increasing intracellular SOD1 expression may be a highly effective approach to decrease the cellular injury that occurs following reperfusion of ischemic tissues.
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PMID:Overexpression of human copper, zinc-superoxide dismutase (SOD1) prevents postischemic injury. 953 76

Oligo-elements such as zinc (Zn), selenium (Se) and copper (Cu) have a significant influence on the function of the immune system. Various immunological and inflammatory changes are known to occur in patients undergoing cardiopulmonary bypass. The aim of this study was to evaluate changes in serum oligo-elements levels during and following cardiopulmonary bypass. The serum levels of Zn, Se and Cu were determined in 67 consecutive patients, with coronary artery disease admitted for coronary artery bypass grafting. Blood samples for oligo-elements, analysis were withdrawn into metal-free tubes just prior to the start of cardiopulmonary bypass; at 30, 60 and 90 min into cardiopulmonary bypass; following weaning from cardiopulmonary bypass; 30 min after termination of cardiopulmonary bypass; at 24 h; and on the 5th postoperative day. Trace elements analyses were performed using atomic absorption spectrophotometry. Interleukin 6 and 8, as well as serum albumin, creatine phosphokinase, lactate dehydrogenase and creatine phosphokinase-MB fractions were also analyzed. The mean age was 63 +/- 9 years and 91% (61) were men. The mean preoperative left ventricular function was 52 +/- 12%, Canadian Cardiovascular Society (CCS) angina class was 3.7 +/- 0.5 and 30% (20) of the operations were re-do's. All patients had normothermic cardiopulmonary bypass. Mean cardiopulmonary bypass-time was 85 +/- 31 min. One patient was lost for the recovery sampling (hospital mortality, 1.5%). Nine patients had a postoperative cardiac index < 2.0 liter/min per m2, which required pharmacological support and additional intra-aortic balloon pump in two of them. Other postoperative complications were few. There was a rapid depletion of S-selenium and S-Zn levels, which were halved at 30 min after cardiopulmonary bypass and remained low throughout the study period. The Cu/Zn ratio increased significantly at the start of cardiopulmonary bypass, which indicated an inflammatory reaction and was not normalized until the 5th postoperative day. Length of ischemia time, presence of diabetes. hypertension and hyperlipidemia did not influence the results, while a prolonged cardiopulmonary bypass-time > 120 min resulted in a higher Cu/Zn ratio than observed for shorter cardiopulmonary bypass-times. This indicates a more profound inflammatory response. Inflammatory parameters responded in the same manner as described earlier by others. These data indicate that severe loss of various oligo elements occur in patients undergoing coronary artery bypass grafting and suggests that a supplementary administration of zinc and perhaps also selenium could be appropriate during cardiopulmonary bypass.
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PMID:Inflammatory response and oligo-element alterations following cardiopulmonary bypass in patients undergoing coronary artery bypass grafting. 972 21


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