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

The extraction of reliable and useful relaxation time data for tissue characterization by NMR requires strict protocols, optimized for each type of biological tissue, which include parameters like storage duration and temperature as well as measurement parameters. Spin-lattice relaxation times in liver tissue vary not only with NMR frequency but also with their "time-after-excision characteristics," while spin-spin relaxation times are almost independent of most parameters which influence T1 at 20 MHz in normal liver tissue (e.g., species, sex, circadian rythm, starvation). T2, however, being more sensitive to water content and pH changes, is well suited for detecting nonspecific tissue alterations (e.g., due to ischemia, chemical toxins). Following the suggestions outlined herein, investigation of at least 120 min of time-after-excision (storage) effects allows the significant distinguishing of various physiological differences in normal liver tissue as well as improvement of early detection of liver pathologies.
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PMID:Liver tissue characterization by in vitro NMR: tissue handling and biological variation. 156 62

Tissue acidosis is an important determinant of cell viability following cerebral ischemia. Because of the heterogeneity of tissue response to metabolic stress, a method for measuring intracellular pH (pHi) that preserves spatial information would be desirable. Histophotometry of the pH indicator dye Neutral red offers such a possibility. The purpose of our study was to determine the distribution of pHi following complete irreversible ischemia and show the correlation of mean pHi measured by Neutral red and [31P]NMR in the same brain. Three rats were studied in the anesthetized state. A pHi range was obtained by total cerebral ischemia at various pre-arrest plasma glucose concentrations. The data show that mean pHi calculated by Neutral red was strongly correlated to pHi determined from [31P]NMR (slope: 0.99 +/- 0.08; P less than 0.001, r2 = 0.96). Within each brain, 80-110 discrete samples were analyzed by histophotometry. The pHi distribution of those samples broadened in those rat brains with greater acidosis, suggesting a heterogeneity of response by the tissue to ischemia and the presence of multiple pHi pools. Our results demonstrate the need to use methods which maintain spatial resolution such as is available with histophotometry.
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PMID:Distribution of intracellular pH in the rat brain cortex after global ischemia as measured by color film histophotometry of neutral red. 157 26

The ideal level of hypothermia during myocardial preservation for cardiac transplantation remains unknown. Therefore 31P-NMR spectroscopy was applied to assess the effect of different preservation temperatures (15 degrees C in group 1, 4 degrees C in group 2) on time dependent changes of myocardial high energy phosphorous compounds during prolonged global ischemia (5 hours in group 1, 8 hours in group 2) and subsequent reperfusion of isolated rat hearts preserved with modified St. Thomas Hospital solution. ATP-depletion during ischemia was slower in group 2 leading to a significant difference in myocardial ATP-concentrations between both groups after 3 hours of ischemia. The drop of intracellular pH during ischemia was significantly less pronounced in hearts preserved at 4 degrees C compared to 15 degrees C. Postischemic recovery of both left ventricular (LV) peak systolic pressure and its +dP/dt max. was superior in group 2, although the ischemic time was 3 hours longer than in group 1. Hypothermia at 4 degrees C appears favourable for prolonged myocardial protection compared to 15 degrees C with regard to preservation of ATP, prevention of intracellular acidosis and postischemic hemodynamic recovery.
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PMID:[31-phosphor-NMR spectroscopy for determining optical preservation temperature during long-term myocardial ischemia]. 158 63

In the conclusion of this series of reports, the application of 31P/2H NMR to investigate the pathophysiology of sepsis in rat hindlimb muscle is demonstrated. Sepsis decreased muscle [PCr] by 18%, 18 +/- 4 SD vs 22 +/- 4 SD mmol/kg tissue wet wt (P = 0.01) in control rats but [ATP] was unchanged, 6 mmol/kg tissue wet wt (P = 0.2). The derived free cytosolic [ADP] in the two groups was similar, [ADP]septic = 0.023 +/- 0.004 SD and [ADP]control = 0.021 +/- 0.003 SD mmol/kg tissue wet wt, and not statistically different (P = 0.14). Likewise [Pi] in the septic and control groups was not statistically different, [Pi]septic = 1.1 +/- 0.5 SD and [Pi]control = 1.2 +/- 0.4 SD mmol/kg tissue wet wt (P = 0.2). Septic rats presented the symptom of respiratory alkalosis evidenced by elevated blood pH. Sepsis decreased muscle blood flow by 33%, P = 0.003, but examination of individual subjects did not demonstrate a correlation with the reduction in [PCr]. Thus, a metabolic energy deficit caused by cellular ischemia/hypoxia is not a likely cause of cellular abnormality in rat hindlimb muscle during sepsis.
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PMID:Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo. III. Alterations of muscle blood flow and metabolism during sepsis. 159 58

31P-nuclear magnetic resonance (31P-NMR) spectroscopy is widely used to monitor sequential changes in the nucleoside triphosphate (NTP) pool in intact tissues. Recently, the validity of this technique to quantitate incremental changes in ATP in heart has been challenged. Accordingly, we compared NTP measured by 31P-NMR and by chemical techniques in isolated isovolumic rat hearts at 16 and 56 min of oxygenated perfusion and in hearts subjected to 28 min of hypoxia, with or without 28 min of reoxygenation, and 12 or 28 min of ischemia, with or without 28 min of reperfusion. NTP content was calculated from 31P-NMR spectra using an external standard. At the end of each protocol the heart was freeze-clamped, and NTP and ATP contents were determined by chemical assay. After 16 min of normoxic perfusion the values for NTP and ATP contents measured by both methods in the same hearts were indistinguishable. Results from all seven experimental conditions show no significant difference between methods (P = 0.262). Thus both methods detect the same incremental change in NTP and ATP.
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PMID:NMR-invisible ATP in heart: fact or fiction? 161 27

Measuring the T1 of the fluorine resonances of perfluorocarbons (PFC) is a unique method for monitoring oxygen tension in vivo. However, because T1 is also temperature sensitive, error in the pO2 determination due to animal-to-animal temperature variation may arise. Pathophysiologic conditions, such as ischemia, where temperature is not known a priori may also introduce error. Thus, measuring the PFC temperature is clearly desirable in order to correct for tissue temperature variations during the pO2 determination. Because the fluorine chemical shift of various fluorinated compounds has a significant temperature dependence, we evaluated the effect of temperature on the chemical shift of the fluorine resonances of perfluorotributylamine (FTBA). A linear relationship was found between chemical shift and temperature in vitro. In addition, the relative FTBA chemical shifts were essentially independent of pO2. Chemical shift temperature measurements in vivo, obtained from a 10 microL FTBA bubble in the preretinal vitreous space of the rabbit eye, were in good agreement (+/- 0.5 degrees C) with thermocouple measurements from the same location. Good agreement between the NMR determined temperature and core body temperature was also found. The implication of such temperature measurements for the ultimate accuracy of the pO2 determination based on PFC T1 measurements is discussed. To the best of our knowledge, this report describes the first absolute temperature measurement in vivo by NMR.
NMR Biomed
PMID:Perfluorocarbon temperature measurements using 19F NMR. 162 66

Cerebral energy metabolism can be measured non-invasively in unanesthetized neonatal rats with 31P NMR spectroscopy. Using this technique, serial changes in high energy phosphates were determined from the right cerebral hemispheres of 7 day postnatal rat pups during a hypoxic-ischemic insult known to produce focal brain injury. During 3 h of hypoxia-ischemia the concentration of ATP dropped to 33 +/- 8% of prehypoxic (baseline) levels, phosphocreatine (PCr)/Pi decreased from 1.5 +/- 0.51 to 0.16 +/- 0.06, while pH decreased nominally by 0.2 units. After 2.5 h of recovery in air, ATP returned to 75 +/- 10% of baseline levels, PCr/Pi rose to 1.1 +/- 0.28, and pH returned to its normal value of 7.16 +/- 0.06. This model was used to test the efficacy of the adenosine deaminase inhibitor, 2-deoxycoformycin (DCF) as a potential neuroprotective drug. The data for the drug- and saline-treated populations were analyzed by integrating ATP and Pi/PCr levels over specific time intervals, expressing it relative to baseline levels, and modeling it with cubic splines. Pretreatment with 500 micrograms/kg DCF shows a small, but statistically significant, preservation of both ATP and phosphorylation potential during hypoxia and initial recovery. Brain water content (edema) at 42 h recovery was apparently associated with both mean ATP and mean Pi/PCr in the last 2 h of hypoxia-ischemia. When ATP fell below 70% of baseline, brain edema was evident at 42 h of recovery. This methodology is suitable for extension to human infants.
NMR Biomed
PMID:31P NMR spectroscopy of perinatal hypoxic-ischemic brain damage: a model to evaluate neuroprotective drugs in immature rats. 164 72

The aim of this study was to determine whether acute changes in [Mg2+]free occur during increased hydrolysis of cytosolic ATP, and whether these changes were of sufficient magnitude to be involved in the modulation of myocardial metabolism. 31P-NMR was used to estimate free cytosolic Mg2+ levels ([Mg2+]free) during hypoxia, isoproterenol stimulation, and graded low-flow ischemia in crystalloid perfused, isovolumic rat hearts. Cytosolic [Mg2+]free was calculated to be 0.73 +/- 0.12 mM in control hearts (100 mmHg hydrostatic pressure, 95% O2, n = 18). Cytosolic [Mg2+]free increased gradually during 10 min periods of hypoxia (65%, 50%, 35%, 5% O2), and 20 min infusions of isoproterenol (0.4, 3.0, 75 nM), to maximum values greater than 250% of control (P less than 0.05). During 8 min periods of graded low-flow ischemia (12.0, 7.2, 5.3, 3.4, and 1.6 ml/min/g), [Mg2+]free did not change significantly. [Mg2+]free displayed an inverse linear correlation with total cytosolic [ATP] during isoproterenol infusion (r = 0.87), and an exponential correlation during hypoxia (r = 0.82). The data indicate that acute changes in cytosolic [Mg2+]free can occur during conditions of net ATP hydrolysis although changes in ATP alone do not appear to be solely responsible for the changes in [Mg2+]free. Since the magnitude of the changes in [Mg2+]free are sufficient to alter equilibria of enzymes such as creatine kinase and myokinase, it is possible that these changes are involved in the acute modulation of myocardial metabolism.
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PMID:Cytosolic free magnesium in stimulated, hypoxic, and underperfused rat heart. 165 49

Using in vivo 1H NMR spectroscopy (1H MRS) and biochemical analysis, the effects of hyperammonemia on cerebral function were studied in three rat models: acute liver ischemia (LIS), administration of urease (UREASE) and administration of methionine sulfoximine (MSO). By means of localization in three dimensions signals were obtained exclusively from the cerebral cortex. Specially developed lineshape correction and fitting methods were used to quantitate the MRS signals. The following concentration changes were observed; a decrease in glutamate and (phospho)choline for all the models; an increase in glutamine in the LIS and UREASE model but a decrease in the MSO model; a marked increase in lactate in the LIS and UREASE group; a tendency to a decrease in N-acetylaspartate in all the models. These changes agree well with the changes in the post-mortem biochemically determined cerebral cortex glutamine and glutamate concentrations. Estimated absolute 1H MRS metabolite concentrations agree well with those obtained by other techniques; cerebral cortex glutamate, however, is underestimated by about 35% by NMR. The present data support the hypothesis that hyperammonemia is associated with a decreased availability of glutamate for neurotransmission.
NMR Biomed 1991 Feb
PMID:The use of in vivo proton NMR to study the effects of hyperammonemia in the rat cerebral cortex. 167 7

At present in vivo NMR spectroscopic studies of brain glutamate and glutamine concentrations relative to encephalopathy have mainly been performed in hepatic encephalopathy (HE). In vivo proton NMR studies were performed in rats with hyperammonemia and acute HE due to acute liver ischemia as well as in rats with hyperammonemia due to either repeated urease i.p. injection or i.p. administration of methionine sulfoximine, a well known inhibitor of glutamine synthetase. In man, in vivo proton NMR is described in patients with chronic liver disease: cirrhosis of different etiology and associated with different degrees of HE. In the experimental models proton NMR spectroscopy of the cerebral cortex revealed an increase in glutamine concentration, a decrease in glutamate concentration and a decrease in phosphocholine compounds. In humans no clear distinction between cerebral cortex glutamate and glutamine concentration could be made by in vivo 1H NMR spectroscopy. However, the combined glutamate/glutamine peak increased in a way compatible with an increased cerebral cortex glutamine concentration during chronic HE. In the cirrhotic patients too a decrease in cerebral cortex phosphocholine compounds was observed, the explanation of which is unclear. Both the experimental work and the clinical observations support the hypothesis that impairment of the glutamate/glutamine cycle between astrocytes and neurons plays a role in the pathogenesis of hepatic encephalopathy.
NMR Biomed 1991 Apr
PMID:What the clinician can learn from MR glutamine/glutamate assays. 167 85


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