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

To investigate the high-energy phosphate metabolic correlates of left ventricular (LV) dysfunction during the onset and recovery from severe, global myocardial ischemia in vivo, seven preinstrumented closed-chest dogs had ECG-gated phosphorus-31 (31P) NMR-spectroscopy (NMR-S) studies performed and LV micromanometer and sonomicrometer data measured before, during, and every 5 min following severe occlusive global myocardial ischemia. Ischemic LV + dP/dtmax fell from 2396 +/- 576 mm Hg/s at baseline to 2185 +/- 478 mm Hg/s (p less than 0.05) and did not normalize until after 30 min of reperfusion. LV ejection fraction (EF) decreased significantly (0.32 +/- 0.07 EF units to 0.12 +/- 0.13 EF units; p less than 0.05) and did not recover by 30 min of reperfusion (0.27 +/- 0.09 units; P less than 0.05 vs baseline). Simultaneous 31P NMR-S studies demonstrated excellent beta-ATP signal-to-noise (10 +/- 4:1). Myocardial acidosis occurred during global ischemia (delta pH = -0.22 +/- 0.23 units; p less than 0.05), with recovery at 30 min of reperfusion. Inorganic phosphate/phosphocreatine ratio (Pi/PCr) increased significantly during ischemia (0.46 +/- 0.07 to 0.61 +/- 0.07; P less than 0.05), with delayed normalization of this ratio at 30 min of reperfusion. beta-ATP peak area did not change during ischemia. Pi/PCr and LV contractility (+dP/dtmax) were significantly correlated at baseline (r = -0.70) and during global ischemia (r = -0.78; p less than 0.01), but not during recovery (r = 0.006; p = NS). Therefore, the simultaneous evaluation of high-fidelity hemodynamic data and topical 31P NMR-S can be performed in the intact state.
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PMID:Simultaneous cardiac mechanics and phosphorus-31 NMR spectroscopy during global myocardial ischemia and reperfusion in the intact dog. 206 6

Two metabolically distinct cell populations were detected when two peaks of inorganic phosphate (Pi), corresponding to two pHi values, were recorded by Phosphorus Magnetic Resonance Spectroscopy (31P MRS). One cell population, having intracellular pH (pHi) values less than 6.3, was thought to contain neither PCr (phosphocreatine) nor ATP and was thus considered metabolically unstable or inactive. The second cell population, having normal or near normal pHi, was considered metabolically active with adequate values of ATP and PCr. We can therefore further analyze the bioenergetics in this cell population. The results were based upon studies of 14 ischemic dogs that were anesthetized with 2% isoflurane and ventilated. The amount of Pi associated with the acidic cell population (low pHi) was used to calculate the fraction of metabolically inactive brain tissues. This value correlated well with the ATP depletion of the total cell population. This suggests that in the acidic cell population, PCr and ATP supplies were depleted by dephosphorylation during ischemia, leading to an accumulation of acidic Pi. In addition, ATP synthesis in this population may be inhibited by the low intracellular pH. On the other hand, the bioenergetic state of the metabolically stable cell population having a nearly neutral pHi changed markedly during ischemia. The PCr/Pi dropped to 0.8 and the phosphorylation potential (PP) dropped to 10 mM-1 from 40 mM-1. With reperfusion, two distinct patterns of responses were observed. One group showed the restoration of ATP (recovery group) whereas the second group did not (non-recovery group). After 3 h of reperfusion, the ATP restored group showed complete recovery of PCr.(ABSTRACT TRUNCATED AT 250 WORDS)
NMR Biomed 1990 Dec
PMID:Metabolic heterogeneity in brain tissue during incomplete ischemia and reperfusion. 209 39

Serial 31P nuclear magnetic resonance spectra were acquired from the brain in 19 rats following microsphere embolization of the right internal carotid artery. The brains were sectioned and stained with 2,3,5-triphenyltetrazoline chloride 6 h post-embolization to visualize infarcted areas. There was a narrow dosage range for the effect of embolism measured by maximum decline in pH at 20 min, mortality, and infarct size. This narrow range effect may be due to occlusion of collateral channels by the 16 micron microspheres. There was a strong correlation between decline in pH at 20 min post-embolization and infarct size (r2 = 0.76); this decline was the best early marker for eventual infarct in our study. This animal model for macroscopically heterogenous brain ischemia may be useful for the evaluation of therapeutic interventions in stroke, and as an aid in the interpretation of phosphorus spectra from mixed volumes of ischemic and non-ischemic brain.
NMR Biomed 1990 Dec
PMID:31P spectroscopy in experimental embolic stroke: correlation with infarct size. 209 41

Dizziness is doubtlessly one of the most common symptoms to arise in ischemia of the brainstem. In such cases the circulatory deficit can not only cause a direct lesion of the vestibular structures but it may also block the compensatory process. There are, however, significant difficulties in establishing whether such dizziness can be attributed to a brainstem insufficiency (BI). In fact, both CAT and NMR provide data only in the case of permanent CNS tissue lesions and tests such as the Doppler examination of neck blood vessels are unable to establish the true state of cerebral blood flow. In order to obtain semi-quantitative data regarding cerebral blood flow 99mTc-HMPAO-S.P.E.T. (Single Photon Emission Tomography) was used in 18 patients suffering from dizziness and for whom there was strong indication that the underlying cause could be vascular. There was a discrepancy between the Doppler and S.P.E.T. findings in 50% of the cases. CAT, however, proved negative in all but one of the cases. These data indicate that Doppler testing of the neck blood vessels can provide useful information regarding the status of the cerebral-afferent vessels but that these cannot be correlated to the level of cerebral blood flow. On the other hand, with S.P.E.T., in 15 of the 18 patients, it proved possible to identify significant alterations in cerebral blood flow in the absence of any permanent tissue lesions as those revealed by CAT and NMR. In the light of the present results cerebral S.P.E.T. appears to be a highly valid tool when, faced with dizziness for which a vascular origin is suspected, one must evaluate cerebral prognosis and therapy.
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PMID:[Use of SPECT in the diagnosis of vertigo syndromes of vascular nature]. 209 69

NMR is still considered essentially, in the field of ischemic brain vascular disease, an imaging method. On the contrary, Authors review MR-spectroscopy possibilities, emphasizing that by this method it is possible to achieve a complete and dynamic study of brain energy metabolism, and therefore to identify markers of cellular injury clearly more sensitive and precocious than MRI morphological findings. Moreover, this method allows to easily evaluate cerebral blood flow, pharmacologic treatment efficacy, effects of eventual metabolic abnormalities on ischemia's evolution.
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PMID:[Role of magnetic resonance spectroscopy in the diagnosis of ischemic cerebrovasculopathy]. 219 46

The brain is a highly differentiated organ, exhibiting a variety of local metabolic and hemodynamic responses to ischemia. Several analytical strategies are useful in characterizing these abnormalities: these include the direct assay of tissue metabolites; topographic methods for depicting regional patterns of NADH, ATP, glucose, lactate, and pH; in vivo spectroscopic methods for analyzing mitochondrial redox state over time; autoradiographic approaches to quantitation of local glucose utilization, blood flow, protein synthesis, and pH; and the noninvasive methods of positron emission tomography and NMR spectroscopy, which are applicable as well to human studies. In focal ischemia, "core" regions of severe blood-flow reductions progress to irreversible injury, while the adjacent "penumbral" zone appears to represent an unstable region threatened with possible injury yet potentially amenable to therapeutic intervention. Glucose utilization in focal ischemia is remarkable for its local heterogeneity and, in the postischemic state, tends to be predictive of local tissue injury. The selective vulnerability of particular brain regions to injury following global ischemia has now been extensively correlated with alterations of local metabolism and hemodynamics. Hyperglycemia is generally deleterious to neuronal survival in ischemia--an effect mediated via tissue lactacidosis. Small differences in brain temperature also profoundly influence ischemic outcome. Areas remote from an ischemic focus may also show metabolic and functional abnormalities--so-called "diaschisis," which may be transneuronally and/or humorally mediated. Multiple neurotransmitters are released during ischemia and interact to influence tissue injury. Regional postischemic hypoperfusion may also influence outcome.
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PMID:Local metabolic responses to cerebral ischemia. 220 95

The application of one-dimensional 31P chemical shift imaging to the study of the isolated perfused rat heart is described. Its applicability for the examination of regional ischemia in the isolated perfused rat heart is demonstrated. The data sets show clearly the localization to the ischemic and nonischemic regions of the heart. Such studies will permit the correlation of cardiac metabolism and function in a controlled manner that is not possible in the application of these techniques to the intact animal. In particular, the time resolution of the experiments will enable spatially localized metabolic studies to be performed during the onset of ischemia and during reperfusion.
NMR Biomed 1990 Aug
PMID:31P chemical shift imaging of the regionally ischemic perfused heart. 220 51

To assess the protective effect of verapamil on ischemic myocardium, the changes in high energy phosphates, inorganic phosphate, and intracellular pH were serially and quantitatively measured in ischemic porcine hearts without collateral circulation using 31P-NMR spectroscopy, together with ultrastructural examination. Twenty-six farm pigs weighing 11 to 14 kg were anesthetized with fluothane and were divided into control (C) group and verapamil pretreatment (V) group. In V group 0.2 mg/kg of verapamil was administered for 20 mins before occlusion of the anterior descending coronary artery. 31P-NMR spectra were serially obtained throughout the experiment, and ultrastructural examination was done at 20-min occlusion and at 120-minute occlusion in each group. At 10-min ischemia, creatine phosphate was significantly preserved in V group (C/V = 11 +/- 4%/16 +/- 5% P less than 0.05). At 20 min ischemia, ATP was significantly preserved (C/V = 60 +/- 9%/73 +/- 8% P less than 0.05), and intracellular pH was significantly higher in V group (C/V = 6.4 +/- 0.2/6.6 +/- 0.1 P less than 0.05). Morphologically, clumping of the nuclear chromatin, mitochondrial swelling and decrease in glycogen were milder in V group at 20 min ischemia. However, these beneficial effects disappeared at 120 min ischemia. Thus pretreatment with verapamil attenuated depletion of high energy phosphates, progression of acidosis, and ultrastructural changes. There was no significant difference of rate pressure product and regional blood flow between hearts with and without pretreatment of verapamil. Therefore, this protective effect may be due to the energy sparing effect or other direct subcellular effect of verapamil on ischemic myocyte.
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PMID:Protective effect of verapamil in ischemic porcine hearts: analysis of ultrastructural and metabolic changes using in vivo 31P-NMR spectroscopy. 223 44

We studied the brain metabolism in macular mutant mice (Ml/y, +/y), an appropriate model of Menkes kinky hair disease, using 31P- and 1H-NMR spectroscopy to clarify the pathophysiological mechanisms of disturbed nervous function. An analysis of in vivo 31P-NMR spectra showed a decreased phosphocreatine (PCr)/inorganic phosphate (Pi) ratio and decreased ATP levels and decreased intracellular pH in Ml/y mice at 9 days, suggesting energy failure in the brain. This associated decline in ATP levels may reflect multiple causative factors including disturbed mitochondrial respiration and ischemia secondary to circulatory failure. Brain metabolites, including PCr, creatine, lactate and 7 amino acids were easily detectable quantitatively and qualitatively by in vitro 1H-NMR spectrum. An elevation in lactate levels and a decline in PCr/creatine ratio in Ml/y mice at 9 days were also noted with an in vitro study, supporting the in vivo data. NMR spectroscopy is a useful and promising tool to obtain the information on brain metabolism.
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PMID:[A pathophysiological study of macular mutant mouse as a model of human Menkes kinky hair disease. II. Analysis of brain metabolism using 31P- and 1H-nuclear magnetic resonance spectroscopy]. 226 Dec 31

ATP concentrations in the perfused rat liver during normoxic perfusion, transient ischemia, and recovery from transient ischemia were measured using the modified 31P cryo-NMR method (Chance, B., Nakase, Y., Bond, M., Leigh, J. S., Jr., and McDonald, G. (1978) Proc. Natl. Acad. Sci. U.S.A. 75, 4925-4929). Transient ischemia was induced in the perfused livers of starved rats, and multiple freeze-trapped tissue samples were taken from each liver at short intervals (15-30 s) during ischemia or following reperfusion. The freeze-trapped tissue was pulverized together with an antifreezing agent and high energy metabolites were measured by 31P NMR at 243 K after thawing. By using the cryo-NMR technique, a biochemical time resolution of 2 s could be achieved. Absolute metabolite concentrations were calculated by comparing the peak areas with internal standards mixed into the samples. Good time resolution and reliable concentration measurements provided by the cryo-NMR method enable us to estimate the ATP synthesis rate in the perfused liver during reperfusion following transient ischemia. The rate of ATP synthesis in the normoxic perfusion was 1.95 mumol/min/g wet weight; the maximal ATP synthesis rate during the recovery phase from ischemia was 5.75 mumol/min/g wet weight.
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PMID:Rate of ATP synthesis in the perfused rat liver by 31P cryo-NMR. 226 13


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