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)

The purpose of this study was to better characterize renal adenine nucleotide pool responses to different forms of shock, contrast the changes to those found in other intra-abdominal organs (the liver and small intestine), and assess whether these changes are closely mimicked by those produced by renal arterial occlusion, the usual method used to study ischemic acute renal failure. Rats were subjected to hemorrhagic shock, septic shock, or cardiopulmonary shock of varying severities and durations. The liver consistently had the greatest energy depletion, followed by the kidney, and then the small intestine. However, only the kidney developed clear morphological damage (S3 brush border sloughing). Kidney adenylate pools were better preserved during septic shock and cardiopulmonary shock than during hemorrhagic shock despite comparable blood pressures. Only profound hemorrhagic shock (35-40 mm Hg for 25 minutes) decreased total adenylate pools (ATP + ADP + AMP). However, the degree of renal catabolite (nucleosides plus purine base) accumulation did not correlate with the amount of renal total adenine nucleotide depletion, partially because circulating catabolites contributed to intrarenal catabolite pools. Purine base/uric acid ratios differed among shocked organs, consistent with different degrees of xanthine oxidase activity (small intestine greater than liver greater than kidney). Renal morphological damage decreased during the immediate (0-30 minutes) postshock period, and the extent of this improvement was not altered by xanthine oxidase inhibition (oxypurinol), suggesting that the immediate postshock period is not one of serious oxidative injury. Shock, in comparison with renal arterial occlusion, caused only modest ATP loss/catabolite accumulation, very low purine base/uric acid ratios, and no immediate-reperfusion (0-30 minutes) resynthesis of the total adenylate pool. Thus, ischemia-induced renal adenylate changes may differ considerably, depending on the nature of the ischemic event.
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PMID:Adenine nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury. 198 61

The Caerphilly Collaborative Heart Disease Study is based on a large cohort of men (2,398) aged 49-66 years at the time of study. Platelet aggregation induced by collagen, thrombin, and ADP was measured in fasting blood samples and was related to prevalent angina, past myocardial infarction, and electrocardiographic evidence of ischemic heart disease. A number of subjects had taken aspirin, other nonsteroidal anti-inflammatory drugs, or other drugs affecting platelet aggregation 7 days before blood sample collection; after the exclusion of these subjects, data were available for 1,811 men. No relations were demonstrated with angina, but significant relations were shown between past myocardial infarctions and electrocardiographic evidence of ischemia and ADP-induced aggregation (both primary and secondary) and between electrocardiographic evidence of ischemia and thrombin-induced aggregation. The strongest relation indicated more than a twofold increase in the odds of a past myocardial infarction in subjects of the highest fifth of ADP-induced primary platelet aggregation compared with the lowest fifth. No significant relations were detected with collagen-induced aggregation. Accounting for a number of possible confounding factors had a relatively small impact on the relations between platelet aggregation and ischemic heart disease. Other evidence, including the well-established effect of aspirin on reducing the incidence of ischemic heart disease, indicates that the relations we describe are unlikely to be simply an effect of IHD on platelets.
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PMID:Ischemic heart disease and platelet aggregation. The Caerphilly Collaborative Heart Disease Study. 198 96

We have developed an isolated perfused tumor model to study the metabolism of solid tumors by nuclear magnetic resonance spectroscopy. Morris hepatomas (7777) were implanted in the inguinal region of Buffalo rats, such that they developed an isolated blood supply. These tumors were perfused with a RBC perfusate, removed from the animal, and studied by 31P nuclear magnetic resonance spectroscopy. ATP levels, as determined from the spectra, were stable for as long as the tumors were maintained in the magnet (7 h) only if the perfusate contained inosine, adenosine, and insulin. The adenosine and inosine were also required for recovery from ischemia. Under these conditions, ischemia did not result in a change in tumor pH. The gamma nucleoside triphosphate resonance was significantly larger than the beta nucleoside triphosphate resonance in spectra of some of the perfused tumors, suggesting that ADP above about 300 nmol/g wet weight was not complexed in these tumors. The adenylate levels determined from extracts, O2 consumption, histology, and 31P nuclear magnetic resonance spectra of extracts of perfused tumors and tumors in situ were all similar, indicating the perfused tumor is a reasonable model of the tumor in vivo.
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PMID:An ex vivo model for the study of tumor metabolism by nuclear magnetic resonance: characterization of the phosphorus-31 spectrum of the isolated perfused Morris hepatoma 7777. 198 24

Assessment of the level of high-energy phosphates in the myocardium before, during and after ischemia was performed in 19 consecutive patients who underwent cardiac operation. The following results were obtained. 1) The levels of total nucleotides (ATP, ADP, AMP, CP) determined before, during and after aortic cross clamp were 14.94 +/- 4.12, 5.59 +/- 2.16 and 3.58 +/- 1.14 micrograms/mg. protein in the right atrial appendage. Those in the left ventricular myocardium were 18.22 +/- 4.90, 6.99 +/- 1.52 and 4.35 +/- 1.06 micrograms/mg. protein. The latter levels were higher than the former. 2) Rapidly decreasing after aortic cross clamp, the nucleotides dropped to 37-38% of preischemic level during aortic cross clamp and to 23% of preischemic level 30 minutes after reperfusion. At the termination of extracorporeal circulation, when circulatory dynamics stabilized, the nucleotides were only recovered to 50-53% of preischemic level. 3) Negative correlation was observed between the length of aortic cross clamp time and the content of nucleotides in the atrial muscle. (p less than 0.05) 4) Fluctuations in the nucleotide level indicated that the current method of myocardial protection using GIK solution produced unsatisfactory recover from ischemic damage and reperfusion injury.
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PMID:[Changes in high-energy phosphates in the myocardium before and after ischemia]. 202 18

Using Percoll density gradient centrifugation, free (nonsynaptosomal) mitochondria were isolated from the dorsal-lateral striatum and paramedian neocortex of rats during complete forebrain ischemia and reperfusion. Mitochondria prepared from either region after 30 min of ischemia showed decreased state 3 (ADP and substrate present) and uncoupled respiration rates (19-45% reductions) with pyruvate plus malate as substrates, whereas state 4 respiration (no ADP present) was preserved. At 6 h of recirculation, state 3 and uncoupled respiration rates for mitochondria from the paramedian neocortex (a region resistant to ischemic damage) were similar to or even increased compared with control values. By contrast, in mitochondria from the dorsal-lateral striatum (a region containing neurons susceptible to global ischemia), decreases in state 3 and uncoupled respiration rates (25 and 30% less than control values) were again observed after 6 h of recirculation. With succinate as respiratory substrate, however, no significant differences from control values were found in either region at this time point. By 24 h of recirculation, respiratory activity with either pyruvate plus malate or succinate was greatly reduced in samples from the dorsal-lateral striatum, probably reflecting complete loss of function in some organelles. In contrast with these marked changes in free mitochondria, the respiratory properties of synaptosomal mitochondria, assessed from measurements in unfractionated homogenates, were unchanged from controls in the dorsal-lateral striatum at each of the time points studied, but showed reductions (19-22%) during ischemia and after 24 h of recirculation in the paramedian neocortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective impairment of respiration in mitochondria isolated from brain subregions following transient forebrain ischemia in the rat. 202 1

The effect of adenosine (ADO) on the recovery of cellular adenine nucleotides (AN) was evaluated in the cultured cells deprived of oxygen and substrates (ischemia) and in nonischemic cells (control). The primary cultured cells were obtained from microdissected rabbit proximal straight tubules. Ten-day-old cultured cells were made ischemic for 6 hr, and allowed to recover for 24 hr. At the end of ischemia, cells were incubated with ADO, theophylline (T), dipyridamole (D), coformycin (C) or combined agents for 3 hr. Total AN (TAN) were determined after 3 and 24 hr of recovery. The results, after 3 hr of incubation, suggest that in both control and ischemic cells, ADO is taken up by cultured cells and is preferentially converted to nucleotides. This effect is blocked by D, which inhibits ADO uptake, uninfluenced by C, which inhibits ADO deaminase and potentiated by T, which inhibits 5'-nucleotidase. After 24 hr of recovery, the beneficial effects of ADO alone or combined D, C, or T, on TAN were not seen in control cells. In contrast, in the ischemic cells, after 24 hr of recovery, ADO + T normalized ATP, ADP and TAN to the preischemic levels. T alone significantly increased ATP after 24 hr of recovery. To demonstrate further that the beneficial effect of T is due to inhibition of 5'-nucleotidase, cells were treated with adenosine alpha, beta-methylene diphosphate in the same manner as T. Combined ADO + adenosine alpha, beta-methylene diphosphate normalized ATP, ADP and TAN after 24 hr of recovery. This finding suggests that inhibition of 5'-nucleotidase improves postischemic AN.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Roles of adenosine and theophylline on the recovery of adenine nucleotides in postischemic cultured renal tubular cells. 203 18

The effect of human superoxide dismutase (h-SOD) on the ischemic heart was studied in the isolated perfused working rat heart. Myocardial mechanical function expressed as pressure-rate product decreased and completely stopped within 5 min after the onset of global ischemia, and never recovered after reperfusion following 20 min of ischemia. In the ischemic myocardium, the levels of ATP, ADP, and creatine phosphate decreased, and those of AMP and lactate increased. Reperfusion of the ischemic heart did not restore the level of ATP completely. When the heart was treated with h-SOD, the perfusion medium was switched from the buffer containing no h-SOD to that containing h-SOD at either 100, 300 or 1,000 units/ml 5 min before the onset of ischemia. The pressure-rate products of the heart treated with 100, 300, and 1,000 units/ml of h-SOD were restored by reperfusion to 22%, 59%, and 51% of the preischemic level, respectively. The levels of ATP and creatine phosphate in the reperfused heart with 300 and 1,000 units/ml of h-SOD were significantly higher than those without h-SOD. However, a dose-response relationship was not observed when h-SOD was used in concentrations greater than 300 units/ml. These results indicate that a certain amount of h-SOD has some beneficial effects on the ischemic myocardium.
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PMID:Effects of human superoxide dismutase on ischemic and reperfused myocardium in isolated perfused rat heart. 204 40

The visibility of ATP and ADP to NMR was studied by comparing simultaneous measurements of freeze-trapped tissue sections from perfused rat liver under normoxia and ischemia using a modified 31P-cryo-NMR method and biochemical assay. The 31P-cryo-NMR method provides good time resolution and allows the quantitation of absolute metabolite concentrations. Prior to 31P-cryo-NMR measurements, freeze-trapped tissues were thawed in the presence of cryoprotectant and EDTA. With this sample preparation procedure, the integrity of the plasma and mitochondrial membranes was not maintained, inducing homogeneous microviscosity and chelation of intracellular divalent cations, thereby increasing the visibility of metabolites compared to the in vivo NMR measurement. With ischemic stress, total cellular ATP concentration decreased significantly (P less than 0.001). While ADP concentrations measured by cryo-NMR and biochemical analysis were consistent during normoxia and ischemia, ATP concentrations measured by cryo-NMR were significantly lower (P less than 0.05) than those obtained by biochemical analysis. The amount of invisible ATP (0.42 +/- 0.10 mumol/g wet weight: mean +/- S.E.) did not change after the induction of ischemia. The results of this study suggest that ATP invisibility to cryo-NMR is not due to compartmentation into regions of high paramagnetic ion concentrations or high microviscosity, but is influenced by other factors.
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PMID:Visibility of ATP and ADP in freeze-trapped tissue from perfused rat liver during normoxia and ischemia using 31P-cryo-NMR. 206 82

Starting from the assumption that tumor cells constantly experience transient ischemia and anoxia, and that this results in metabolic stress which is reflected above all, on the concentration of ATP, ADP and AMP, in other words, the adenine nucleotide pool (AdN), the aim of our research was to study the degradation and resynthesis kinetics of that pool on two types of malignant cells. All experiments were conducted in vitro with cells of the transplantable tumors of Ehrlich's ascitic carcinoma and the AS 30D hepatoma, and metabolite analyses were carried out enzymatically or by way of the HPLC chromatography method. It was found that immediately after the setting on of anoxia, there comes not only to a fall in ATP, but also to a fall in the complete adenine nucleotide pool for about 50%. The further maintenance of anaerobiosis does not have a significant influence on the AdN pool. The adenine nucleotide pool resynthesis is very rapid in the examined cells, and in the presence of glutamine and inosine, there comes to an occurrence of its significant growth. Evidence is given that the resynthesis in Ehrlich's ascitic carcinoma cells is made possible through the purine nucleotide cycle, which probably brings about the intensive glutamine oxidation and aspartate production, while in the AS 30D hepatoma cells it develops by means of adenosine kinase. The AS 30D hepatoma cells maintain a high ATP level in the absence of oxygen for a long time, provided that iodine-acetate is not added, which points to the fact that they have some other kind of energetic reserve aside from ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Kinetics of degradation and resynthesis of the adenine-nucleotide pool in tumor cells]. 209 81

Reports on enhanced nucleotide regeneration by purines during reperfusion are conflicting. We have, therefore, evaluated the effects of inosine or adenine, administered after ischemia, on adenine nucleotide levels and function in isolated rat hearts. The hearts were perfused with a Tyrode solution, containing 10 mM D-glucose, with or without 5 mM pyruvate. After 15 minutes without flow, the hearts were reperfused for 45 minutes with 20 microM purine and 0.5 mM D-ribose. Adenine nucleotide levels tended to recover better in the purine-treated groups. The purines decreased the ATP/ADP ratio by 10-15% (p less than 0.05) if pyruvate was absent. The IMP level in the inosine/glucose group exceeded that in all other groups by a factor of two (p less than 0.001). Inosine increased the adenosine concentration in the effluent sixfold (p less than 0.005). The hypoxanthine concentration rose up to four times following adenine treatment (p less than 0.05). The administration of purine, with or without pyruvate, did not affect mechanical recovery, heart rate or coronary flow. We conclude that inosine and adenine failed to improve cardiac function and hardly affected nucleotide levels in the reperfused heart.
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PMID:Effects of inosine and adenine on nucleotide levels in the post-ischemic rat heart, perfused with and without pyruvate. 210 91


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