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

Human blood is a very complex tissue. Therefore the idea of rediscovery its different cellular and plasmatic constituents would seem to be utopic. To be efficient the oxygen carrier, be it natural or by synthesis, must be stripped of antigenicity, be easily stockable and transportable. Thus these properties permit its use in urgent circumstances (accidents, natural disasters, war...), in those countries where there is a non existent or limited transfusional structure. This, under certain conditions, during very specific pathologies (localised ischemia for example). Among several hypotheses, they are two main lines of research that of "hemoglobin solutions" the oldest and the most physiological. This will be developed here in more lengthy terms due to our personal work on the subject. The second line of research concerns fluorocarbons, the most modern and artificial and without doubt better known to doctors and the public. 1. HEMOGLOBIN SOLUTIONS. Other than nephrotoxicity, which has proved affordable, research han revealed four large limitations with hemoglobin solutions (a high affinity for oxygen due to absence or loss of 2.3 DPG, a short half life due to vascular loss, rapid dimerisation and elimination of urine, insufficient concentration of prepared solutions (70 g/L) with as a result a weak oncotic pressure and oxygen supply, oxidation in methemoglobin). In order to overcome the two inconveniences, proposals were made to modify hemoglobin chemically, the idea coming from the putting into operation of potential analogues to or substitutes for 2.3 DPG which it is advisable to bring or to keep--by covalent bonding--near to the fixation site of the natural ligand. Thus our group has already deposed several patents and is now working on a complex hemoglobin-dextran benzine tetracarboxylate which appears promising. Today, due to the quality and reproduction of the results obtained on animals with chemically modified hemoglobin preparations clinical assays should be carried out soon. 2. FLUOROCARBONS. In this very different approach which uses totally synthetic compounds oxygen carrying can only be realised in dissolved form. Due to this fluorocarbons, even though they are remarkable solvents of gas, do not reach their full efficiency unless the patient breathes in a very rich oxygen atmosphere. This is therefore a considerable limiting factor. The other big problem is the insolubility of these compounds and therefore the need to emulsify them, but unfortunately these emulsions are difficult, if not impossible to stabilise.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Artificial blood in 1990: from a lifelong dream to today's reality]. 208 28

40 patients with ischemic heart disease were studied. In 60% of them a higher content of HbA2 was found. These data for higher frequency of HbA2 among the patients with ischemic heart disease do not correspond with the average incidence of the genetically determined anomaly A2-beta-thalassemia among the Bulgarian population. The negative data for increased methemoglobin, the shift of the oxygen dissociation curve to the right toward increased oxygen release from the hemoglobin molecule, the normalization of HbA2 after several days, the lack of anomalous fraction in the analyses lead to the conclusion that HbA2 plays a compensatory role in patients with ischemic heart disease and its dynamic changes could be used as a diagnostic test for ischemia.
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PMID:[Changes in the hemoglobin A2 level of patients with ischemic heart disease]. 247 9

To compare the effects of hypoxia and ischemia on left ventricular (LV) diastolic function, we studied 17 isolated, isovolumic dog hearts by measuring LV diastolic chamber distensibility (LV end diastolic pressure at constant volume), wall thickness, and myocardial pH in response to hypoxia at constant coronary flow or pressure versus global ischemia (zero coronary blood flow). Hypoxic perfusates consisted of methemoglobin-containing red blood cells suspended in lactated Ringer's solution. Brief cross-clamping of the coronary perfusion line was used to assess the contribution of coronary turgor to chamber distensibility and wall thickness. With hypoxia, left ventricles showed a significant early (5 minutes) decrease in diastolic distensibility and an increase in wall thickness, at either constant coronary perfusion pressure or flow. The increase in wall thickness was independent of hypoxia-induced changes in coronary turgor. In contrast, global ischemia produced an early increase in LV diastolic chamber distensibility and a decrease in wall thickness. When global ischemia was continued beyond 60 minutes, a decrease in LV chamber distensibility developed. This diastolic contracture was not associated with an increase in LV wall thickness. Myocardial pH decreased slightly during 15 minutes of hypoxia and markedly with 15 minutes of global ischemia. Thus, LV diastolic chamber distensibility decreased during 15 minutes of hypoxia, while an increase in distensibility was seen during global ischemia of similar duration. During hypoxia, these changes were associated with increased LV wall thickness, at either constant coronary perfusion pressure or constant coronary flow. Prolonged ischemia led to diastolic contracture without an increase in wall thickness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative effects of hypoxia and ischemia in the isolated, blood-perfused dog heart: evaluation of left ventricular diastolic chamber distensibility and wall thickness. 290 95

This investigation studies the toxicity of heme proteins and/or their break-down products on renal function. Heme proteinemia precedes acute tubule necrosis at a frequency great enough to suggest a causal relationship between the two events. Physiological and metabolic functions of kidney slices are investigated in several models of acute tubule necrosis. Organic acid and organic base transport is depressed earliest. These alterations in tubule function cannot be explained by ischemia or obstruction alone. Heme proteinemia in rats or incubation of renal slices in medium containing heme proteins yields several interesting observations. Neither in vivo or in vitro do hemoglobin and methemoglobin alone produce a depressive effect on the transport systems studied. However, parallel to many clinical situations, when such secondary insults as hypoxia and elevated ammonia concentrations are included in the experimental design, transport functions are depressed. Ferrihemate, a molecule smaller than hemoglobin or methemoglobin, depresses transport function without secondary insults. From these studies it is concluded that heme proteins play a role in tubule dysfunction seen in acute tubule necrosis. A model is presented that collates these data with other factors known to play a part in the pathogenesis of this renal syndrome.
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PMID:Evaluation of the renal toxicity of heme proteins and their derivatives: a role in the genesis of acute tubule necrosis. 541 25

NADPH-dependent methemoglobin reductase, first detected in erythrocytes sixty years ago, has subsequently been purified and characterized as a methylene blue reductase and a flavin reductase. The reductase plays no role in methemoglobin reduction under normal conditions, but its activity serves as the basis for the treatment of methemoglobinemia with methylene blue or flavin. On-going studies demonstrate that this cytosolic protein is also present in liver and that its primary structure distinguishes it from other known proteins. The bovine erythrocyte reductase tightly binds hemes, porphyrins, and fatty acids with resulting loss of activity. Pyrroloquinoline quinone serves as a high-affinity substrate of the reductase, suggesting that this naturally-occurring compound may be a physiological substrate. The ability of the reductase to catalyze the intracellular reduction of administered riboflavin to dihydroriboflavin suggested that this system might be exploited to protect tissues from oxidative damage. This hypothesis was supported by our finding that dihydroriboflavin reacts rapidly with Fe(IV)O and Fe(V)O oxidation states of hemeproteins, states that have been implicated in tissue damage associated with ischemia and reperfusion. Preliminary studies demonstrate that, as predicted, administration of low concentrations of riboflavin protects isolated rabbit heart from reoxygenation injury, rat lung from injury resulting from systemic activation of complement, and rat brain from damage caused by four hours of ischemia. Data from these animal studies suggest that flavin therapy holds promise in protecting tissue from the oxidative injuries of myocardial infarction, acute lung injury, stroke, and a number of other clinical conditions.
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PMID:Evidence that NADPH-dependent methemoglobin reductase and administered riboflavin protect tissues from oxidative injury. 841 88

Two magnetization transfer (MT) contrast effects, a T2-like effect and the improved contrast observed when gadolinium is used with MT, are combined in a single sequence. Forty patients (22 males:18 females; mean age, 45 years (23-87)) with suspected intracranial pathology underwent MRI on a 1.5 Tesla system. Of 46 lesions; seven were ischemic, five infective, seven neoplastic, four hemorrhagic, four multiple sclerosis, seven human immunodeficiency virus (HIV) leukoencephalopathy, nine normal/miscellaneous, and three gliosis. A conventional spin-echo sequence (TR 900 TE 15) was used with on-resonance binomial MT pulses. The sequence was performed postgadolinium +/- MT. The signal intensity ratios +/- MT were: white matter, 0.62 +/- 0.03; gray matter, 0.75 +/- 0.04; ischemia, edema, and demyelination, 0.75 (0.57-0.86); and gadolinium/methemoglobin, 0.85 (0.81-0.98). Areas which exhibited MT had T2-like contrast and those that did not maintained expected contrast for the given parameters. The result was a combination of T2-like contrast, gadolinium enhancement, and dark cerebrospinal fluid (CSF) providing both increased sensitivity to lesions which exhibited both contrast features and improved delineation of periventricular lesions. Furthermore, the differential signal between T2-like contrast of edema and gadolinium enhancement in neoplastic or infective lesions was maintained.
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PMID:Clinical utility of a new contrast option from magnetization transfer contrast. 857 39

Despite years of research, delayed cerebral vasospasm remains a serious complication of subarachnoid hemorrhage (SAH). Recently, it has been proposed that endothelin-1 (ET-1) mediates vasospasm. The authors examined this hypothesis in a series of experiments. In a primate model of SAH, serial ET-1 levels were measured in samples from the perivascular space by using a microdialysis technique and in cerebrospinal fluid (CSF) and plasma during the development and resolution of delayed vasospasm. To determine whether elevated ET-1 production was a direct cause of vasospasm or acted secondary to ischemia, the authors also measured ET-1 levels in plasma and CSF after transient cerebral ischemia. To elucidate the source of ET-1, they measured its production in cultures of endothelial cells and astrocytes exposed to oxyhemoglobin (10 microM), methemoglobin (10 microM), or hypoxia (11% oxygen). There was no correlation between the perivascular levels of ET-1 and the development of vasospasm or its resolution. Cerebrospinal fluid and plasma levels of ET-1 were not affected by vasospasm (CSF ET-1 levels were 9.3 +/- 2.2 pg/ml and ET-1 plasma levels were 1.2 +/- 0.6 pg/ml) before SAH and remained unchanged when vasospasm developed (7.1 +/- 1.7 pg/ml in CSF and 2.7 +/- 1.5 pg/ml in plasma). Transient cerebral ischemia evoked an increase of ET-1 levels in CSF (1 +/- 0.4 pg/ml at the occlusion vs. 3.1 +/- 0.6 pg/ml 4 hours after reperfusion; p < 0.05), which returned to normal (0.7 +/- 0.3 pg/ml) after 24 hours. Endothelial cells and astrocytes in culture showed inhibition of ET-1 production 6 hours after exposure to hemoglobins. Hypoxia inhibited ET-1 release by endothelial cells at 24 hours (6.4 +/- 0.8 pg/ml vs. 0.1 +/- 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05) and at 48 hours (6.4 +/- 0.6 pg/ml vs. 0 +/- 0.1 pg/ml, control vs. hypoxic endothelial cells; p < 0.05), but in astrocytes hypoxia induced an increase of ET-1 at 6 hours (1.5 +/- 0.6 vs. 6.4 +/- 1.1 pg/ml, control vs. hypoxic astrocytes; p < 0.05). Endothelin-1 is released from astrocytes, but not endothelial cells, during hypoxia and is released from the brain after transient ischemia. There is no relationship between ET-1 and vasospasm in vivo or between ET-1 and oxyhemoglobin, a putative agent of vasospasm, in vitro. The increase in ET-1 levels in CSF after SAH from a ruptured intracranial aneurysm appears to be the result of cerebral ischemia rather than reflecting the cause of cerebral vasospasm.
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PMID:Source and cause of endothelin-1 release into cerebrospinal fluid after subarachnoid hemorrhage. 925 95

Sickle cell anemia (SCA) is a disease caused by production of abnormal hemoglobin, which binds with other abnormal hemoglobin molecules within the red blood cell to cause rigid deformation of the cell. This deformation impairs the ability of the cell to pass through small vascular channels; sludging and congestion of vascular beds may result, followed by tissue ischemia and infarction. Infarction is common throughout the body in the patient with SCA, and it is responsible for the earliest clinical manifestation, the acute pain crisis, which is thought to result from marrow infarction. Over time, such insults result in medullary bone infarcts and epiphyseal osteonecrosis. In the brain, white matter and gray matter infarcts are seen, causing cognitive impairment and functional neurologic deficits. The lungs are also commonly affected, with infarcts, emboli (from marrow infarcts and fat necrosis), and a markedly increased propensity for pneumonia. The liver, spleen, and kidney may experience infarction as well. An unusual but life-threatening complication of SCA is sequestration syndrome, wherein a considerable amount of the intravascular volume is sequestered in an organ (usually the spleen), causing vascular collapse; its pathogenesis is unknown. Finally, because the red blood cells are abnormal, they are removed from the circulation, resulting in a hemolytic anemia. For the patient with SCA, however, the ischemic complications of the disease far outweigh the anemia in clinical importance.
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PMID:Sickle cell anemia. 1145 73

Melatonin has been shown to act as a radical scavenger in various chemical and biological model systems in vitro. Kinetic evidence is now provided showing that melatonin inhibits the irreversible degradation of hemoglobin (Hb), when incubated with red blood cells exposed to the oxidant activity of cumene hydroperoxide (cumOOH). A decrease of heme loss and accumulation of soluble methemoglobin (met-Hb) are explained in terms of the interaction of the indoleamine with perferryl Hb (Hb[Fe(IV)=O]), a highly reactive Hb-derived radical species responsible for the irreversible Hb degradation. A kinetic study, in pure chemical solution, showed that melatonin can effectively reduce the oxoferryl heme group of perferryl-Hb, thus forming met-Hb. The reducing activity of melatonin is of the same order as that of Trolox, the water-soluble vitamin E analog. This novel radical-scavenging activity of melatonin may contribute to the previously observed protective effects of melatonin in ischemia-reperfusion injury.
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PMID:Reaction of melatonin with hemoglobin-derived oxoferryl radicals and inhibition of the hydroperoxide-induced hemoglobin denaturation in red blood cells. 1155 66

Sickle cell anemia is a disease caused by production of abnormal hemoglobin, which binds with other abnormal hemoglobin molecules within the red blood cell to cause rigid deformation of the cell. This deformation impairs the ability of the cell to pass through small vascular channels. Sludging and congestion of vascular beds may result, followed by tissue ischemia and infarction. Liver injury can be caused by the adherence of deformed or hemolyzed erythrocytes to hepatic vascular endothelium. Adhesion of large numbers of hemolyzed red blood cells to hepatic macrophages, or occlusion of hepatic sinusoids by fragmented red cells, can also result in injury of the liver. Chronic intrahepatic cholestasis is an uncommon complication in patients with sickle cell disease. The findings in this case suggest that therapeutic erythrocyte apheresis may benefit patients who have unusual complications of sickle cell disease, such as chronic intrahepatic cholestasis in the liver.
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PMID:Sickle cell anemia connected with chronic intrahepatic cholestasis: a case report. 1465 71


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