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)

It is generally assumed that myocardial adenine nucleotides are broken down (e.g., during ischemia) via AMP----adenosine----inosine, but contribution of the pathway AMP----IMP----inosine cannot be excluded. The catabolism of exogenously added adenosine (1-20 microM) was studied in isolated rat hearts. All catabolites (i.e., inosine, hypoxanthine, xanthine, and uric acid) were measured together with nonmetabolized adenosine. Even at low (1 microM) adenosine concentrations, deamination accounted for 60% of adenosine disappearing from the perfusate. The adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) (5 and 50 microM) was infused together with adenosine (5 microM). These two concentrations of EHNA inhibited deamination of exogenous adenosine by 65 and 91%, respectively. When hearts were made ischemic by reduction of perfusion pressure, addition of EHNA raised the adenosine release from 1.4 to 9.8 nmole/min per gram wet wt., but surprisingly, the release of inosine and oxypurines (8 nmole/min per g wet wt.) did not change. These results suggest that considerable breakdown of myocardial adenine nucleotides can occur via the AMP----IMP----inosine pathway instead of AMP----adenosine----inosine. The rate of total purine release is probably not a good measure of intracellular adenosine formation.
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PMID:Adenosine deaminase inhibition and myocardial adenosine metabolism during ischemia. 399 44

In this study evidence is provided to suggest that nucleoside formation with hypoxia in myocardial tissue from the guinea-pig follows a different course from that in the rat, rabbit or dog. 1) After ischemia, tissue levels of adenosine remain barely detectable in the guinea-pig but rise considerably in the rat and the dog. 2) IMP, remaining almost absent in the dog, does not change in the rat but strongly increases (X 6) in the guinea-pig heart with ischemia. 3) Mioflazine, a nucleoside transport inhibitor, completely reverses the ratio adenosine/inosine in dog myocardium after 8 min of ischemia, making adenosine by far the major nucleoside. No effect could be detected in the guinea-pig. 4) In contrast with the rat and rabbit, ischemia in the guinea-pig does not lead to any considerable release of adenosine upon reperfusion. 5) In the rabbit, the presence of a nucleoside transport inhibitor completely reverses the adenosine/inosine ratio in reperfusates after ischemia. Although the release is strongly inhibited under these conditions in the guinea-pig, adenosine release remains negligible when compared with inosine. 6) Even in the presence of high concentrations of an adenosine deaminase inhibitor, inosine remains the major metabolite released upon reperfusion after ischemia, in the guinea-pig heart.
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PMID:Formation and release of nucleosides in the ischemic myocardium. Is the guinea-pig the exception? 409 81

Phosphatic metabolite (perchloric acid extractable) concentrations of cerebral tissues were analyzed by phosphorus-31 nuclear magnetic resonance (P-31 NMR) spectroscopy following external perfusion of the isolated rat brain (30 min or 60 min) under the following conditions: (a) constant perfusion pressure with either fluorocarbon- or erythrocyte-based medium, and (b) constant perfusate flow rate (3 ml/min) with the erythrocyte-based medium. Metabolite concentrations of control perfused brains were compared with those in nonperfused controls to provide a basis for detecting any qualitative or quantitative changes in cerebral metabolite composition. Metabolic responses of perfused brains to ischemia (incomplete ischemia, 83% reduction in flow for 10 min; transient complete ischemia for 1.5 or 2 min) were evaluated immediately after the ischemic episode and at selected time points during reperfusion (3 and 15 min). Alterations in cerebral metabolite levels induced by hypoxia were analyzed using a nonperfused rat brain model. Irrespective of the perfusion method employed, the phosphatic metabolites of control perfused rat brains were identical quantitatively to those of the nonperfused controls. Cerebral ischemia resulted in significantly increased levels of ADP, AMP + IMP, Pi, fructose 1,6-diphosphate, and glycerol 3-phosphate (global ischemia only), whereas ATP and phosphocreatine (PCr) levels declined significantly. The magnitude of these changes varied with the severity of the ischemia; however, following 15 min of control reperfusion metabolite levels had reverted to preischemic values. Significant perturbations in tissue phosphoethanolamine (3.84 delta resonance) content were evident at various time points during ischemia and postischemic recovery, which varied according to the perfusion conditions. In contrast to the changes observed in response to ischemia, hypoxia affected only cerebral high-energy phosphate levels. ATP and PCr levels were reduced, while a concomitant, essentially equimolar, increase in Pi and ADP was observed. The present studies indicate that in terms of phosphatic metabolites, the control equilibrated isolated perfused rat brain is quantitatively and qualitatively indistinguishable from the nonperfused rat brain in vivo regardless of the perfusion conditions (constant flow versus constant pressure). The metabolic responses to ischemia and hypoxia, as measured by P-31 NMR, were consistent with the pattern of changes reported elsewhere. Overall, P-31 NMR spectroscopic evaluation of the intact rat brain provides a potential experimental context for dynamic measures of cerebral metabolism under exogenously controlled conditions. Th
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PMID:P-31 nuclear magnetic resonance analysis of brain: II. Effects of oxygen deprivation on isolated perfused and nonperfused rat brain. 609 45

Metabolic changes in the myocardial adenine and hypoxanthine pools of isolated rat hearts subjected to global ischemia, hypocalcemic global ischemia, and global substrate-free anoxia were compared. At timed intervals between 0 and 60 min separate aliquots of extracts of the ventricles were used to determine either tissue pH, or the components of the adenine pool and their catabolites by reverse phase high performance liquid chromatography (HPLC). The coronary perfusate draining from anoxically perfused hearts was collected over perchloric acid, neutralised and chromatographed by HPLC. The development of left ventricular resting tension (contracture) was recorded in the three groups of hearts. After 60 min ischemia the major catabolites, (AMP, inosine and hypoxanthine) comprised 70% of the total pool (11, 7 and 4 mumol/g dry wt, respectively). After the same period of anoxia 50% of the total pool, comprising adenosine, inosine, hypoxanthine and uric acid in approximately equal proportions, was recovered from the coronary perfusate. The major products remaining in the tissue were IMP and, to a lesser extent AMP (8 and 5 mumol/g dry wt, respectively). Left ventricular contracture developed at different rates in the three groups of hearts but always correlated closely with the maximum rate of adenine pool catabolism. The loss of components from the tissue and the divergence in pathway from adenosine to IMP production which occurs during anoxic perfusion should possibly be considered when assessing the biochemical events occurring in regionally ischemic heart muscle with significant residual flow.
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PMID:Adenine pool catabolism in the ischemic, the calcium-depleted ischemic, and the substrate free anoxic isolated rat heart: relationship to contracture development. 653 18

The major pathway of purine catabolism in mouse kidney during ischemia occurs through IMP, inosine, hypoxanthine, and xanthine. Short periods of ischemia (reversible cell injury) allow a rapid return of the energy charge to control values and a rapid return of ATP and GTP to value of 60-70% of control. ATP and GTP then slowly return to control levels over the next 24 h. Long periods of ischemia (irreversible cell injury; ischemic times longer than 1 h) allow a gradual return of the energy charge to control levels. ATP, GTP or total adenine or guanine nucleotides do not return to control levels even after 24 h of reinfusion under these circumstances. We conclude that irreversibly injured kidney cells retain the ability to phosphorylate purine nucleotides, but lose the ability to restore the concentrations of the purine nucleotides to control values.
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PMID:Recovery of nucleotide levels after cell injury. 723 28

We tested the hypothesis that residual oxygen supply during acute low-flow ischaemia or hypoxemia is a major regulator of myocardial performance, metabolism and recovery. Rat hearts were exposed for 20 min to either ischemia (coronary flow reduced to 10% of baseline), hypoxemia (oxygen content reduced to 10% baseline) or a "mixed" condition (combined ischaemia and hypoxemia). The oxygen supply (coronary flow x oxygen content) was matched in all groups (n = 16 per group). Hypoxemic hearts had the highest performance (systolic and developed pressures, +/- dP/dtmax and oxygen uptake) and content of IMP and AMP. Ischaemic hearts had the highest content of ATP, phosphocreatine, adenine nucleotides and purines. As flow and/or oxygenation were restored, post-ischemic hearts showed better functional and metabolic recovery than post-hypoxemic ones. "Mixed" hearts were more similar to hypoxemic ones during oxygen shortage but to ischemic ones during recovery. We conclude that as oxygenation is critically limiting, coronary flow is relatively more important than oxygen supply in determining myocardial function, metabolism and recovery, most likely secondary to changes in the metabolism of diffusible substances.
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PMID:Myocardial metabolism and function in acutely ischemic and hypoxemic isolated rat hearts. 747 79

Arteriovenous malformations (AVMs) are usually associated with diminished cerebral blood flow (CBF) in the parenchyma surrounding AVMs because of the steal phenomenon. Vasoreactivity in the parenchyma surrounding AVMs may change because of ischemia and abnormal hemodynamics. The aim of this study was to investigate vasoreactivity in parenchyma surrounding AVMs. Quantitative single-photon emission computed tomography using N-isopropyl-p-I-123 iodoamphetamine (IMP-SPECT) was performed before and after intravenous administration of acetazolamide (Diamox). Diamox is a potent cerebral vasodilator which causes tissue acidosis, and IMP-SPECT was performed 10 min after intravenous infusion of a 1g dose. The subjects were 8 patients with AVMs. The AVM was in the frontal lobe in 3 patients, the temporal lobe in 1 patient, the lateral ventricle in 1 patient, the midbrain in 1 patient, the basal ganglionic region in 1 patient, and the vein of Galen in 1 patient. A rotating gamma camera with two heads was used to perform SPECT. IMP was injected into an arm vein, and a 5-min period of blood withdrawal, 1 ml/min, was started simultaneously from a small catheter placed in the radial artery. Kuhl's method was used to quantify cerebral blood flow (CBF). Multiple contiguous 6-pixel-diameter region of interest (ROI) circles along the cerebral cortex and cerebellar hemisphere were used, and ROIs which included the AVM nidus, draining veins or infarctions were excluded from the study. Vascular territories containing arteries feeding the AVM were defined as near-ROIs on SPECT, and all other ROIs were defined as far-ROIs. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Vasoreactivity of normal brain tissue in cases of arteriovenous malformations--evaluation by 123I-IMP SPECT using acetazolamide]. 761 85

A study was performed to compare the follow-up results of superficial temporal artery-middle cerebral artery anastomosis between a group of nine elderly patients (aged 70 years or over) and another group of 24 non-elderly patients (aged less than 70 years) with cerebral ischemia. The 33 patients, comprising 26 males and seven females, were evaluated pre- and postoperatively by four-vessel angiography, CT scan, MRI and cerebral blood flow (CBF) examination using either xenon inhalation or 123I-IMP SPECT. In some patients, additional evaluations were done. For those with dementia, the minimental scale (MMS), P300 event-related potential, the Hachinski ischemia score, and the vowel word counting test (Kaneko's KANAHIROI) were used, and for the hemiplegic, the Barthel index indicating ability of daily life (ADL) was employed. The results of follow-up for periods ranging from 12 to 55 months were "excellent" (returned to previous job) or "good" (able to perform self-care) in 27 of the 33 patients (81.8%) including six (66.6%) of the elderly group and 21 (87.5%) of the non-elderly group. There was no significant difference between the two groups by statistical evaluation. Among the nine patients with dementia (five under 70, four 70 years of age or over), eight (four under 70, four 70 or over) showed "rapid recovery" with improved postoperative MMS, P300, vowel word counting score and CBF. One patient under 70 (Case 5; a 47-year-old male) with a delayed 2-day recovery from general anesthesia, took as long as 6 months to obtain the self-care ability in daily life. Excluding this patient, all of the remaining eight patients responded quickly to surgery and were able to go home with their families after 2 to 4 weeks, there being no significant difference between the two age groups. In the 14 patients with hemiplegia/paresis (nine under 70, five 70 or over), a definitely better result was obtained for the non-elderly group. Eight of the nine non-elderly patients (89%) showed full ADL (Barthel index 100), whereas only one of three elderly patients (33.3%) showed almost full ADL (Barthel index 97). In five progressive stroke patients, (three under 70, two 70 or over) ultra-early bypass was performed within 8 hours postictus. Definitely better results were obtained in the patients aged less than 70, who showed rapid recovery and were able to return to their previous jobs 1 to 3 months after surgery. In contrast, the two patients aged 70 or over showed no improvement. In this report, we discuss the clinical and physiological variables that may be important for selection of elderly patients for cerebrovascular bypass surgery.
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PMID:[Results of superficial temporal artery-middle cerebral artery anastomosis for elderly and non-elderly patients with cerebral ischemia]. 782 13

Localized 1H magnetic resonance spectroscopy was performed in a 45-year-old woman with migraine. She developed throbbing headache attacks without aura since thirteen years ago and the attack was accompanied with right hemiplegia since seven years ago. Brain MRI showed no abnormalities and 123I-IMP SPECT revealed mild frontal dominant decrease of cerebral blood flow. It seemed that her condition was positioned between migraine with prolonged aura and migrainous infarction of complicated migraine in the classification of International Headache Society. Spectra obtained from bilateral frontal lobe interictally showed elevation of lactate at left side. Choline, creatine, and N-acetyl-aspartate were almost equal on both side. The above results suggest that slight ischemia which is not detected by MRI is present or there is a disturbance of oxidative glycolysis, which is induced by mitochondrial dysfunction.
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PMID:[Elevation of cerebral lactate detected by localized 1H magnetic resonance spectroscopy in a patient with migraine]. 792 68

We report the results of a prospective follow-up study which was designed to identify the sequential change of regional vasodilatory capacity and its relation to long-term prognosis in patients with atherothrombotic brain ischemia. We evaluated a total of 139 acetazolamide tests using 123I-IMP SPECT in 76 patients with occlusion or greater than 75% stenosis of the carotid or middle cerebral arteries. Reduced vasodilatory capacity was demonstrated in 34 patients (44.7%) at entry. Patients were divided into two groups on the basis of the initial acetazolamide test, i.e., impaired and non-impaired group. All patients were prospectively followed for 28.4 +/- 15.9 (Mean +/- S.D.) months and acetazolamide tests were repeated every 1-2 years. Follow-up acetazolamide tests demonstrated normalization of impaired vasodilatory capacity in 14 patients, including 12 without surgical revascularization. The survival analysis comparing the two groups for all strokes and all death, and for ipsilateral ischemic strokes and all death did not demonstrate the poor prognosis of imparied group. However, the recurrence of ischemic stroke was found in 4 out of 8 cases without improvement of vasodilatory capacity. The present data indicate that the sequential evaluation of vasodilatory capacity is of importance in the clinical management of patients with major cerebral artery occlusion or severe stenosis.
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PMID:[Long-term prognosis and blood flow reactivity to acetazolamide in atherothrombotic brain ischemia]. 831 88


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