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)

Oxygen affinity of hemoglobin, erythrocyte 2,3-diphosphoglycerate (DPG) and adenosine triphosphate (ATP) concentrations were compared before and after oral administration of vinpocetine (TCV-3B) (15 mg/d), a primarily vasodilating agent, for three weeks in eight patients with vascular dementia of the Biswanger type which is characterized by diffuse myelin pallor and multiple lacunes in the cerebral white matter. After vinpocetine administration, oxygen affinity of hemoglobin (P50) was significantly increased (26.5 +/- 0.55 to 27.6 +/- 0.62 mmHg; mean and standard deviation, p less than 0.05), red blood cell (RBC) ATP concentrations were significantly increased (846 +/- 168 to 1,158 +/- 130 mumol/l RBC, p less than 0.05), while DPG concentrations were unaltered (4.46 +/- 0.48 to 4.59 +/- 0.57 mmol/l RBC). There was a significant positive correlation between the increase of P50 and the increase of erythrocyte ATP concentrations (r = 0.67, p less than 0.05). The effect of vinpocetine of enhancing oxygen release of hemoglobin may offer an additional benefit to its primary vasodilating action in the treatment of vascular dementia of the Binswanger type due to chronic ischemia.
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PMID:Effect of vinpocetine on oxygen release of hemoglobin and erythrocyte organic polyphosphate concentrations in patients with vascular dementia of the Binswanger type. 239 97

In acute myocardial infarction the effect of oxygen administration in modifying infarct size is uncertain. To evaluate this as well as the effects of moderate hypocarbia, four groups of anesthetized dogs were studied experimentally for 2 hours after coronary branch ligation: group I (controls; room air, normal blood gases): group IIA (FIo2 50%, normal Paco2); group IIB (FIo2 50%, low Paco2); and group IIC (50% oxygen given after ligation, normal Paco2). In addition to hemodynamics, the effect of differing blood gas patterns on hemoglobin-oxygen affinity (P50) and ischemic alterations of myocardial electrolyte and water content were evaluated. Hemodynamic changes among the four groups included decreases in LV ejection fraction and cardiac output. The latter was more pronounced in the oxygen treated groups with proportionately greater increases in systemic resistance. P50 increased in all groups, indicating decreased hemoglobin-oxygen affinity; in group IIC this increase was significantly greater than in group I. In all groups an analysis of central and border areas of myocardial ischemia showed loss of potassium and gain of sodium and water, but no beneficial effect on this result by oxygen administration pre or post ligation could be demonstrated. On the contrary, among those dogs administered oxygen the ischemic changes appeared more pronounced than in the control group. Moderate hypocarbia did not modify the myocardial electrolyte and water change. The results of this study do not support the hypothesis that oxygen administration can favorably modify the myocardial changes of ischemia, at least early in the course of myocardial infarction.
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PMID:Effects of oxygen administration and alteration in arterial PCO2 on ischemic myocardial changes following experimental coronary artery ligation. 681 24

Reducing blood oxygen affinity may enhance myocardial oxygen delivery during ischemia. We evaluated this hypothesis in awake, previously instrumented dogs that received a 20 ml/kg infusion of a solution of dihydroxyacetone, phosphate, and pyruvate after acute occlusion of either the left anterior descending or circumflex coronary artery. This infusion reduced blood oxygen affinity (BOA) after 2 hours; the P50 increased from 29.9 +/- 0.7 torr (mean +/- SD) to 32.1 +/- 0.6 torr; P less than 0.01 (BOA group). Four dogs received 20 ml/kg of phosphate and pyruvate solution to assess volume effects (V group), and five dogs were controls (C group). The 2-hour P50 values in V and C were unchanged. Regional flow (15-mum spheres) reduction 2 hours postocclusion was compared to the percent tissue infarcted determined by histology 7-9 days after occlusion for multiple samples from the endocardial layer of the left ventricle. When flow was less than 40% of normal, V and C had 55% infarction while BOA had 37% (P less than 0.05); at flow less than 20% of normal, V and C had 79% infarction while BOA had 38% (P less than 0.001); and at less than 10% of normal, V and C 87% and 94% infarction, respectively, while BOA had 56% (P less than 0.001). Reducing blood oxygen affinity after coronary artery occlusion significantly decreased the extent of myocardial necrosis for the same degree of ischemia. Reducing BOA may increase oxygen delivery to ischemic myocardium when flow is restricted.
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PMID:Improvement in the relationship between flow to ischemic myocardium and the extent of necrosis with glycolytic intermediates that decrease blood oxygen affinity in dogs. 724 76

Affinity of hemoglobin (Hb) for O2 determines in part the rate of O2 diffusion from capillaries to myocytes by altering capillary PO2. We hypothesized that a decrease in Hb O2 affinity (increased P50) would increase capillary and tissue PO2 (PtiO2) and improve O2 consumption during ischemia. To test this hypothesis, blood flow to the pump-perfused left hindlimb of 18 anesthetized and paralyzed dogs was progressively decreased over 90 min while hindlimb O2 consumption and O2 delivery (QO2) and PtiO2 were measured at the muscle surface. Arterial PO2 was maintained at 150 +/- 10 Torr in all dogs. We increased P50 by 12.3 +/- 0.9 (SE) Torr in nine dogs with RSR-13, an allosteric modifier of Hb. This decreased arterial O2 saturation to 90-92% but increased mean PtiO2 from 35.5 +/- 11.6 to 44.1 +/- 15.2 (SD) Torr (P < 0.05) with no change in controls (n = 9). O2 extraction ratio at critical QO2 was 74 +/- 2% in controls and 79 +/- 1% in RSR-13-treated dogs (P = not significant). PtiO2 was 30-40% higher in the RSR-13-treated group at any QO2 above critical but did not differ between groups below critical QO2. Perfusion heterogeneity and convergence of the dissociation curves near critical QO2 may have mitigated any effect of increased P50 on O2 diffusion. Still, increasing P50 by 12 Torr with RSR-13 significantly increased PtiO2 at QO2 values above critical.
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PMID:Raising P50 increases tissue PO2 in canine skeletal muscle but does not affect critical O2 extraction ratio. 937 39

The purpose of this work was to investigate the temporal relationship between intensity changes in T2*-weighted NMR images and tissue oxygen content, measured by myoglobin proton NMR spectroscopy, in the skeletal muscle. During an ischemic stress test, the calf muscles of five healthy volunteers were studied at 3 Tesla. An interleaved NMRI-NMRS sequence was used, which made it possible to record T2*-weighted images and myoglobin spectra simultaneously. During ischemia, rapid changes in muscle signal intensity were observed on T2*-weighted images, which immediately preceded myoglobin desaturation. Bearing in mind the respective P50 of hemoglobin and myoglobin, this observation clearly favored the hypothesis that hemoglobin desaturation was responsible for the changes in T2*. This interpretation was further supported by the temporal coincidence between the experimental NMR data and a model of hemoglobin desaturation solely derived from physiological considerations.
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PMID:Evidence of muscle BOLD effect revealed by simultaneous interleaved gradient-echo NMRI and myoglobin NMRS during leg ischemia. 977 72

The red blood cell (RBC) membrane may be reversibly opened using a lysis-resealing continuous flow method. The technology was adapted to the internalisation of an allosteric effector of haemoglobin, Inositol-Hexaphosphate (IHP). This molecule, occupying the allosteric site of 2,3 Bis-Phosphoglycerate with a very large affinity, induces a rightward shift of the oxyhaemoglobin dissociation curve (ODC). From ODC parameters in human volunteers, the potential effect of P50 (oxygen pressure at 50% haemoglobin saturation) on oxygen exchangeable fraction (OEF%), for various oxygen partial pressures (oxemia) was evaluated. For hyperoxic or normoxic arterial oxygen pressure (paO2), rightward shift greatly improved OEF%. In optimised conditions, engineered erythrocytes were potentially able to deliver two to three times more oxygen than normal cells. For patients with decreased paO2, as observed in chronic obstructive pulmonary deficiency (COPD), the reduction in arterial oxygen saturation (saO2%) reduces the benefit of the treatment for paO2 values between 60 and 80 mmHg. Below 60 mmHg, the saO2% reduction cannot be compensated by a corresponding reduction in svO2%, particularly for organs with physiologically low svO2%. In these organs, deleterious effects could be observed for a very large rightward shift of the ODC. Such engineered cells have unique properties for oxygen transport improvement and may be used for the treatment of patients suffering from diseases associated with hypoxia and ischemia.
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PMID:Engineered erythrocytes: influence of P50 rightward shift and oxemia on oxygen transport to tissues. 1019 38

We sought to determine whether neonatal rats that sustain unilateral cerebral hypoxic-ischemic or excitotoxic insults (1) manifest contralateral sensorimotor deficits during development or in adulthood and (2) recover from those deficits. Seven-day-old (P7) rats received a right intrastriatal injection of the glutamate analog N-methyl-D-aspartate (NMDA). Unilateral hypoxia-ischemia (HI) was induced by right carotid ligation followed by 1.5 h in 8% O2. Both procedures produce neuronal loss in the striatum and sensorimotor cortex. Nonlesioned controls were included. We scored percent forepaw placement on the edge of a horizontal surface, with lateral vibrissa stimulation, from P9 to P19, and at P33 and P50. Then, on P50, rats were treated with the NMDA antagonist MK-801 to determine whether deficits could be reinstated. NMDA- and HI-lesioned rats exhibited a deficit in contralateral vibrissa-stimulated forepaw placing that emerged during the second week of life. Yet, by P33 and P50, the lesioned groups and controls were indistinguishable. MK-801 injection on P50 resulted in transient reinstatement of the placing deficit. After unilateral neonatal excitotoxic or HI brain injury, contralateral sensorimotor deficits are detected, but in many animals, these deficits have resolved by adulthood. Thus, timing of sensorimotor tests may influence their sensitivity for detection of focal neuropathology originating in the neonatal period.
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PMID:Early appearance of functional deficits after neonatal excitotoxic and hypoxic-ischemic injury: fragile recovery after development and role of the NMDA receptor. 1264 Jan 81

The initial response to an ischemic event is the rapid release of excitatory amino acid's followed by the activation of the "ischemic cascade". It has been suggested that neurosteroids, which act as negative modulators of excitatory amino acid receptors, may improve behavioral functions and promote neuronal survival following ischemia. The present study evaluated the pharmacological effects of 3-alpha-ol-5-beta-pregnan-20-one hemisuccinate (ABHS), a neurosteroid that inhibits excitatory amino acid receptor function, in a rabbit reversible spinal cord ischemia model (RSCIM). ABHS was administered (25 mg/kg) intravenously (i.v.) 5 or 30 min following the start of occlusion to groups of rabbits exposed to ischemia induced by temporary occlusion of the infrarenal aorta. The group P50 represents the duration of ischemia (min) associated with a 50% probability of resultant permanent paraplegia. Quantal analysis indicated that the P50 of the control group was 23.44 +/- 4.32 min. Using the RSCIM, neuroprotection is observed if a drug significantly prolongs the P50 compared to the control group. Treatment with ABHS (25 mg/kg) 5 min post-occlusion significantly (p < 0.05) prolonged the P50 of the group to 49.18 +/- 10.44 min, an increase of 110%. The effect of ABHS was not durable following a single injection since a significant difference between the control and ABHS-treated groups was not measurable at 48 h. However, if ABHS was injected 5 min following the start of ischemia and again 24 h after ischemia, there was a persistent effect of the drug at 48 h. Moreover, ABHS also increased the tolerance to ischemia if administered 30 min following the start of occlusion. Our results suggest that neuroactive steroids such as ABHS, which are selective NMDA receptor antagonists, may have substantial therapeutic benefit for the treatment of ischemic injuries including spinal cord neurodegeneration and stroke.
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PMID:The neuroactive steroid 3-alpha-ol-5-beta-pregnan-20-one hemisuccinate, a selective NMDA receptor antagonist improves behavioral performance following spinal cord ischemia. 1470 67

Hypothermia decreases cerebral metabolism and increases hemoglobin oxygen affinity. A hypothesis that the reversal of increased oxygen affinity would further attenuate hypothermic cerebral ischemia was tested by evaluating the effects of liposome-encapsulated hemoglobin (LipoHb) with low oxygen affinity (P50 = 40-50 mmHg) on hypothermic incomplete cerebral ischemia. Wistar rats were randomly assigned to one of the following two groups: (A) exchange transfusion with LipoHb solution (Hb = 6 g/dl) (LipoHb, n = 5), (B) no exchange transfusion (control, n = 5). After surface cooling to 22 degrees C, forebrain ischemia was induced for 15 min by bilateral carotid artery occlusion combined with a decrease in the mean arterial pressure (MAP) to 40 mmHg. (31)P-magnetic resonance spectroscopy was performed during ischemia and 45 min of reperfusion. After reperfusion, MAP was significantly higher in the control group than in the LipoHb group (P < 0.01), although there were no significant differences during ischemia. Intracellular pH and phosphocreatine (PCr) levels decreased during ischemia and returned to the preischemic level in both groups following reperfusion. The LipoHb group had a significantly larger decrease and smaller recovery in PCr than the control group (P < 0.0001). Althouth beta-adenosine triphosphate decreased during ischemia in the LipoHb group, it increased in the control group (P < 0.0001). Inorganic phosphate (Pi) increased during ischemia and decreased to the normal value after reperfusion. The LipoHb group experienced a significantly larger production of Pi than the control group (P = 0.02). Hemodilution with high-P50 LipoHb does not reduce ischemic energy depletion induced by hypothermic incomplete forebrain ischemia in rats.
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PMID:Hemodilution with liposome-encapsulated low-oxygen-affinity hemoglobin does not attenuate hypothermic cerebral ischemia in rats. 1636 25

In this study, we evaluated the efficacy of transcranial motor-evoked potentials (tc-MEPs), compared with segmental spinal cord-evoked potentials (SCEPs), for detecting spinal cord ischemia (SCI) and assessed the relationship between neurological outcome and tc-MEPs or SCEPs in the rat aortic occlusion model. In the rats, SCI was induced by aortic occlusion for 10 min with a balloon catheter. At first, tc-MEPs (Group A: n = 6) or segmental SCEPs (Group B: n = 6) was recorded during SCI. Second, in using the quantal bioassay for the relationship between an interval of aortic occlusion and the probability of positive response in tc-MEPs or segmental SCEPs, the P50(MEP) and P50(SCEP) which represent the interval of aortic occlusion associated with 50% probability of assessment of ischemic spinal cord dysfunction by tc-MEP and SCEP were analyzed. The amplitude of tc-MEPs decreased significantly at 30 s and disappeared completely at 2 min after aortic occlusion. In Group B, it took about 6 min after aortic occlusion to diminish SCEP signal amplitude by approximately 50%. P50(MEP) obtained in the quantal analysis was 0.3 +/- 0.1 min. P50(SCEP) was calculated as 6.2 +/- 0.5 min that was significantly (P < 0.01) longer than P50(MEP). Our data indicated that tc-MEP monitoring could detect the onset of SCI so rapidly in comparison with segmental SCEP monitoring, which could provide therapeutic windows in a surgical approach that includes spinal cord protection.
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PMID:Transcranial motor-evoked potentials monitoring can detect spinal cord ischemia more rapidly than spinal cord-evoked potentials monitoring during aortic occlusion in rats. 1680 74


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