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

Persistent alterations in cellular energy homeostasis may contribute to the brain damage that evolves from perinatal cerebral hypoxia-ischemia. Accordingly, the presence and extent of perturbations in high-energy phosphate reserves were analyzed during hypoxia-ischemia and the early recovery period in the immature rat. Seven-day postnatal rats were subjected to unilateral common carotid artery ligation and hypoxia with 8% oxygen at 37 degrees C for 3 h, an insult that produces damage (selective neuronal necrosis or infarction) of the cerebral hemisphere ipsilateral to the common carotid artery ligation in 92% of animals. Rat pups were quick frozen in liquid nitrogen during hypoxia-ischemia and at 10, 30, and 60 min and 4 and 24 h of recovery for enzymatic, fluorometric analysis of phosphocreatine (PCr), creatine, ATP, ADP, and AMP. During hypoxia-ischemia, PCr, ATP, and total adenine nucleotides were decreased by 87, 72, and 50% of control, respectively. During recovery, PCr, ATP, and total adenine nucleotides exhibited a rapid (within 10 min) although incomplete and heterogeneous recovery that persisted for at least 24 h. Mean values for PCr remained between 55 and 85% of control, whereas ATP values remained between 57 and 67% of control. Individual ATP values were inversely related to tissue water content at 10 min of recovery, indicating a close correlation between failure of energy restoration and the extent of cerebral edema as a reflection of brain damage. Thus high-energy phosphate reserves display lingering alterations during recovery from hypoxia-ischemia. The interanimal variability in energy restoration presumably reflects the spectrum of brain damage seen in this model of perinatal cerebral hypoxia-ischemia.
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PMID:Cerebral energy metabolism during hypoxia-ischemia and early recovery in immature rats. 155 74

We used 31P and 1H nuclear magnetic resonance spectroscopy to measure intracellular pH, high energy phosphates, and lactate levels in hearts of turtles (Chrysemys picta bellii) subjected to 1.5 h of global ischemia followed by reperfusion. We simultaneously monitored maximum ventricular developed pressure (Pmax), maximal rate of pressure development (dP/dtmax), rate-pressure product (RPP), cardiac output, and heart rate and also measured lactate efflux from the hearts during reperfusion. Our goal was to test the hypothesis that turtle hearts would prove tolerant of prolonged global ischemia at 20 degrees C and would recover completely on reperfusion without any indication of ischemia-or reperfusion-related injury. The 1.5 h of ischemia resulted in decreases in phosphocreatine and ATP to 31.4 +/- 2.8 and 87.3 +/- 6.3% of control, respectively, while Pi rose to 236.6 +/- 26.3%. Intracellular pH decreased during this period from 7.38 +/- 0.02 to 6.87 +/- 0.04. Most of these changes occurred during the first 30 min. Tissue lactate rose during 1.5 h of ischemia from approximately 1.5 to 22.3 mumol/g wet tissue wt. However, the rate of lactate production was much higher during the first 21 min of ischemia (0.41 mumol.g-1.min-1) than during the remaining 70 min (0.10 mumol.g-1.min-1). With the onset of ischemia, Pmax, dP/dtmax, RPP, and heart rate all decreased dramatically with roughly the same time course as the changes in high-energy phosphates and intracellular pH. On reperfusion, turtle hearts rapidly restored high-energy phosphates, intracellular pH, lactate, and cardiodynamics to control levels, usually within 15-30 min, with no evidence of reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic and cardiodynamic responses of isolated turtle hearts to ischemia and reperfusion. 155 14

Global blood flow (TBF), tumor vascular resistance, laser Doppler flow in superficial tumor areas, and mean arterial blood pressure were evaluated in rats bearing s.c. DS sarcomas. Measurements were performed before and after i.v. administration of rhTNF-alpha 2 or recombinant human lymphotoxin (rhLT) (1 mg/kg). Upon application of the cytokines a significant drop in TBF was found at t greater than or equal to 90 min with a stronger action following rhLT than rhTNF-alpha. At relatively constant mean arterial blood pressure values following the cytokine injection, the microcirculatory function in the tumor periphery was found to be impaired somewhat earlier than TBF, indicating that the cytokines do not preferentially act on the poorly perfused tumor center in the model chosen. This finding is inconsistent with previous histological studies on murine tumors. Acute flow changes encompassed only substantial reductions (i.e., hypoperfusion) rather than a complete ischemia. TBF was slightly increased during the first hour following rhLT whereas after rhTNF-alpha a continuous drop was observed. This differential response could not be observed during laser Doppler flowmetry. Tumor vascular resistance changes largely reflected alterations in TBF. 31P-Nuclear magnetic resonance spectroscopy on murine Meth-A fibrosarcomas revealed dose- and time-dependent decreases of ATP/Pi and phosphocreatine/Pi ratios following i.v. administration of rhTNF-alpha. From comparisons of dose-response curves rhLT appears to be more detrimental than rhTNF-alpha with respect to the bioenergetic status. The observed changes in tumor energy metabolism are similar to those described for TBF. It may therefore be concluded that most of the cytokine effects on the bioenergetic status are secondary to the inhibition of the microcirculatory function. As a major causative factor for the latter, an arterial hypotension can be excluded in the tumor model chosen.
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PMID:Acute effects of tumor necrosis factor alpha or lymphotoxin on global blood flow, laser Doppler flux, and bioenergetic status of subcutaneous rodent tumors. 155 20

The effects of hyperglycemia on the time course of changes in cerebral energy metabolite concentrations and intracellular pH were measured by nuclear magnetic resonance (NMR) spectroscopy in rats subjected to temporary complete brain ischemia. Interleaved 31P and 1H NMR spectra were obtained every 5 min before, during, and for 2 h after a 30-min bilateral carotid occlusion preceded by permanent occlusion of the basilar artery. The findings were compared with free fatty acid and excitatory amino acid levels as well as with cations and water content in funnel-frozen brain specimens. One hour before occlusion, nine rats received 50% glucose (12 ml/kg i.p.) and five received 7% saline (12 ml/kg i.p.). Before ischemia, there were no differences in cerebral metabolite levels or pH between hyperglycemic rats and controls. During the carotid occlusion, the lactate/N-acetylaspartate (Lac/NAA) peak ratio was higher (0.73-1.48 vs. 0.56-0.82; p less than 0.05) and pH was lower (less than 6.0 vs. 6.45 +/- 0.05; p less than 0.05) in the hyperglycemic rats than in the controls. Phosphocreatine and adenosine triphosphate were totally depleted in both groups. Within 5-15 min after the onset of reperfusion, the Lac/NAA peak ratio increased further in all rats; however, only in extremely hyperglycemic rats (serum glucose greater than 960 mg/dl) did the lactic acidosis progress rather than recover later during reperfusion. Total free fatty acid and excitatory amino acid levels, but not cation concentration or water content, in brain correlated with serum glucose levels during and after ischemia and with NMR findings after 2 h of reperfusion. Although profound hyperglycemia (serum glucose of 970-1,650 mg/dl) appears to be associated with progression of anaerobic glycolysis and failure of cerebral energy metabolism to recover after temporary complete brain ischemia and with postischemic excitotoxic and lipolytic reactions thought to participate in delayed cellular injury, severe hyperglycemia (490-720 mg/dl) was associated with recovery of energy metabolism.
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PMID:Effects of hyperglycemia on the time course of changes in energy metabolism and pH during global cerebral ischemia and reperfusion in rats: correlation of 1H and 31P NMR spectroscopy with fatty acid and excitatory amino acid levels. 156 39

Difficulties in studying myocardial metabolism with adequate time resolution have led to contradictory conclusions regarding the mechanisms causing contractile abnormalities during the early stages of ischemia. In acutely instrumented swine, we investigated whether abnormalities in subendocardial ATP, phosphocreatine, or lactate content develop rapidly enough during the first few heart beats after onset of partial myocardial ischemia to contribute to contractile failure. Within the first 15 beats of a 40-50% reduction in left anterior descending coronary artery blood flow, regional myocardial function was significantly reduced but continuing to deteriorate. Rapidly frozen transmural left ventricular biopsies obtained on the 15th heart beat (+/- 1.5 beats) after the onset of ischemia revealed significant decrements in subendocardial phosphocreatine and ATP levels to 77% (p less than 0.05) and 84% (p less than 0.005) of control values, respectively, but minimal change in lactate content. Metabolic effects as assessed by transmural averages took longer to become detectable; thus, there was a tendency to underestimate the importance of subendocardial metabolic effects on myocardial function. When left ventricular preload was assessed during this early time period, left ventricular end-diastolic wall thickness only decreased by 3%, and left ventricular end-diastolic pressure did not change significantly despite a large fall in coronary perfusion pressure. Thus, in an in vivo pig model with techniques optimized to detect subendocardial metabolic changes within the period of very early moderate myocardial ischemia, abnormalities in high energy phosphate compounds occurred rapidly enough to contribute to developing myocardial dysfunction, whereas preload-mediated mechanisms related to vascular distending pressure could not explain the functional deterioration under these conditions.
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PMID:Energy metabolism and contractile function after 15 beats of moderate myocardial ischemia. 157 34

An experimental model of optic nerve ischemia was designed in the rabbit to determine early biochemical alterations, i.e.--changes of high energy phosphate metabolites (ATP and phosphocreatine)--in occlusive and peri-occlusive areas. Vascular occlusion provoked a rapid fall of ATP and phosphocreatine in the optic nerve. Free radicals scavengers, superoxide dismutase plus catalase or dimethylthiourea were able to counteract the drop of phosphate metabolites in the peri-occlusive area. These results show that hypoxia leads to oxygen-derived free radical generation which can be responsible for cell damage and emphasize the role of free radicals in the pathogenesis of ocular diseases related to vascular dysfunction.
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PMID:Alterations of energetic metabolite levels by free radicals during optic nerve ischemia. 158 50

The aim of this work was to ascertain whether free radicals play a causal role in the injury occurring in myocardial ischemia and reperfusion. To this purpose we observed whether spin-trapping compounds protect the heart when used at a concentration capable of reacting with free radicals. The lipophilic spin trap alpha-phenyl-t-butyl nitrone (PBN) was used because it is taken up by the myocites. Isolated Langendorff rat hearts were subjected to ischemia according to two schemes: "Model A" = 30 min zero-flow ischemia followed by 30 min reperfusion; "Model B" = 60 min of low-flow ischemia (10% of the individual value; N2 saturated) followed by 30 min reperfusion. Treated groups received in addition 5.0 mM PBN which was supplied continuously. The following parameters were measured throughout the experiment: contractile performance (RPP); coronary flow (CF); CPK; phosphocreatine (PCr), ATP, inorganic phosphate (Pi), intracellular pH (pHi). The pathology obtained by "Model A" is more severe than that of Model B, and partly irreversible. During the ischemic phase in "Model A", contractility, PCr and ATP dropped to near zero; during initial reflow CPK rose about 13-fold and Pi rose 2.5-fold, while pHi decreased to 6.1. During reperfusion, a partial recovery of PCr, Pi and pHi was observed, while RPP and ATP did not increase; PBN treatment improved significantly PCr and CPK, while the other parameters were unaffected. During ischemia, "Model B" hearts showed a drop of contractility to near zero, of PCr to 35%, of ATP to 50%; CPK rose 7-fold and Pi 1.5-fold; pHi was not modified. During reperfusion, all parameters recovered in part, with exception of Pi. PBN developed a marked protective activity on all tested parameters, which gained a nearly normal value. The results of the present investigations show that the lipophilic spin trap PBN partly protects the heart from the ischemia/reperfusion injury, thus confirming that free radicals play a causal role in this pathology; the continuous loading of the tissue with the drug can be an important factor for obtaining the protective effect.
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PMID:Protective activity of the spin trap tert-butyl-alpha-phenyl nitrone (PBN) in reperfused rat heart. 161 68

The energy metabolism of the right ventricle (RV) in vivo has been largely unexplored. The goal of this study was to develop and implement techniques for in vivo 31P nuclear magnetic resonance (NMR) spectroscopy of the RV free wall. A two-turn, crossover-design elliptical surface coil was constructed to provide high sensitivity across the thin RV wall but minimal sensitivity in the blood-filled RV cavity. In 36 open-chest, anesthetized pigs, 31P spectroscopy of the RV free wall was performed with this coil at a field strength of 2 Tesla. Spectra were obtained from 800 acquisitions in 24 min with an average signal-to-noise ratio of 13.2 for phosphocreatine (PCr). The PCr-to-ATP (PCr/ATP) ratio of porcine RV was 1.42 +/- 0.05 (mean +/- SE), uncorrected for saturation at a repetition time of 1.8 s. With the use of literature values of the time constant of longitudinal relaxation (T1) to correct for partial saturation, the RV PCr/ATP was estimated to lie between 1.7 and 2.3. Decreased RV PCr/ATP was observed during RV ischemia and pressure overload. Thus in vivo 31P spectroscopy of the RV is readily accomplished with an appropriate surface coil and can provide new information about RV energy metabolism.
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PMID:In vivo 31P-NMR spectroscopy of right ventricle in pigs. 162 52

We have isolated, from newborn rats, heart cultures enriched in contractile muscle cells (M) and cultures of fibroblast-like cells (F). M cultures respond to simulated ischemia by an arrest of beating activity, by a decrease in beta oxydation rate, ATP and phosphocreatine content and by a loss of membrane phospholipids associated with neutral lipids accumulation. F cells in contrast do not respond to oxygen deprivation. Firstly, we observed that cocultures of M and F cells respond to oxygen deprivation by an arrest of beating activity and a decrease in cellular ATP content, but failed to exhibit any significant loss of membrane phospholipids. Secondly, we demonstrated that culture medium conditioned by F cells is able to inhibit the reaction of M cells to simulated ischemia thus suggesting that fibroblasts produce a diffusible factor able to block phospholipase activation. Heat treatment and trypsinisation failed to abolish this activity, indicating that the phospholipase inhibitory factor is probably not a polypeptide.
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PMID:Regulation of membrane phospholipid metabolism in heart cell culture. 163 76

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.
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PMID:31P NMR spectroscopy of perinatal hypoxic-ischemic brain damage: a model to evaluate neuroprotective drugs in immature rats. 164 72


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