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

Nuclear magnetic resonance (NMR) spectroscopy detects only free, unbound metabolites. We have therefore compared the free high-energy phosphate content of isolated perfused rat hearts (determined by 31P-NMR) with the total high-energy phosphates of the same hearts (determined by chemical analysis) to determine the fractions, if any, that are NMR invisible. Aerobic perfusion (40 min at 37 degrees C, Pi-free Krebs buffer) was followed by 10, 14, or 18 min total global ischemia and 30 min reperfusion (n = 6 in each group). Fully relaxed 31P-NMR spectra (40 scans using 90 degrees pulses at 15-s intervals) were collected at various times throughout the protocol, and the signal intensities of the beta-phosphate of ATP, phosphocreatine (PCr), and Pi were quantified using methylenediphosphonate as an external standard. Hearts were freeze clamped either before ischemia or at the end of reperfusion and were chemically assayed for ATP, PCr, and Pi. After 40 min of normoxia, the ATP and PCr contents determined by NMR were almost identical to the values determined by chemical analysis. However, only 39 +/- 8% of the total Pi was NMR visible. After reperfusion, after 14 or 18 min of ischemia, the proportion of NMR-visible ATP had decreased to 64 +/- 9% (P less than 0.005). After reperfusion after 18 min ischemia, the proportion of NMR-visible Pi had increased to 76 +/- 10% (P less than 0.05). In conclusion, whereas the total cellular content of PCr is always NMR visible, ischemia-reperfusion can alter the fraction of NMR-visible ATP and Pi.
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PMID:NMR-visible ATP and Pi in normoxic and reperfused rat hearts: a quantitative study. 199 10

Until now, the ischemic tolerance of muscle tissue has not been adequately understood. Even when muscle vitality is lost, the perfusion matrix of the muscle flaps is retained. Because of toxic decomposition, however, irreversibly damaged muscle cells almost certainly increase the rate of complications. The retention of the vitality of the transplanted muscle tissue is absolutely essential for the myokinetic substitute operations, currently in the development stage, involving the free transplantation of muscles. Investigations into vitality reserves were carried out on skeletal muscle specimens. Nuclear magnetic resonance spectroscopy was used to establish that, in ischemia, the ATP pool remained topped up to a large extent as long as phosphocreatine was available. As long as the ATP pool was retained, rearterialization led to the complete restoration of the essential preischemic metabolite concentrations. After the ATP had been exhausted, biochemical restitution through arterial reperfusion did not occur. The time by which the established vitality threshold was reached because of the loss of the ATP pool is called the critical ischemia time; it depends on muscle temperature. The critical ischemia time of human skeletal muscles was determined between 26 degrees and 38 degrees C. A normothermia of 34 degrees C yielded a critical ischemia time of 2.25 hours, which is shorter than that previously reported in the literature. An ischemic tolerance of 5 hours presupposes a muscle temperature of less than 26 degrees C.
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PMID:Ischemic tolerance of human skeletal muscle. 199 17

We determined whether the rate of metabolic recovery and electrophysiological deficit after incomplete cerebral ischemia is related to intracellular pH (pHi) achieved at the end of ischemia in a dose-dependent manner. End-ischemic pHi was varied by employing two ischemic durations, 12 and 30 min, and by setting preischemic plasma glucose to approximately 80 or 400 mg/dl. Incomplete global ischemia was produced in anesthetized dogs by transient intracranial hypertension followed by 4 h of reperfusion, and pHi, ATP, and phosphocreatine (PCr) were measured with 31P magnetic resonance spectroscopy. Cerebral blood flow was reduced to approximately 6 ml.min-1.100 g-1 during ischemia. End-ischemic pHi was greater than 5.7 in all animals from various treatment groups except for four of seven dogs treated with 30-min hyperglycemic ischemia. When end-ischemic pHi remained greater than 5.7, there was nearly complete recovery of ATP, PCr, pHi, intracellular bicarbonate concentration [( HCO3-]i), and O2 consumption. Partial recovery of somatosensory-evoked potentials (SEP) occurred in most of these animals. In the 30-min hyperglycemic animals in which pHi fell below 5.5, ATP, PCr, and O2 consumption recovered by only one-half over 60 min of reperfusion and then declined to near-zero levels without SEP recovery. In addition, pHi remained less than 6.0, and [HCO3-]i remained less than 2 mM throughout reperfusion. We conclude that there is an apparent in vivo pHi threshold of approximately 5.5-5.7 during incomplete cerebral ischemia that is associated with an inability to significantly restore pHi and [HCO3-]i and with secondary deterioration of high-energy phosphate levels.
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PMID:Dependence of cerebral energy phosphate and evoked potential recovery on end-ischemic pH. 199 96

Using a highly specific assay that minimizes enzyme inactivation in vitro, we found that rabbit myocardial tissue contained low levels of xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity that were effectively inhibited by pretreatment of hearts with allopurinol. In parallel, allopurinol treatment also improved ventricular developed pressure, peak systolic pressure, and coronary flow in isolated hearts subjected to 30 min of normothermic global ischemia and 30 min of reperfusion. Although function was protected by allopurinol treatment, creatine kinase (CK) release was not altered by allopurinol. Inhibition of myocardial XO with allopurinol did not increase myocardial ATP or phosphocreatine. In addition, allopurinol did not scavenge superoxide anion or hydrogen peroxide in vitro. The results support the possibility that relatively low amounts of XO activity, similar to levels reported in human myocardium, may contribute to cardiac ischemia-reperfusion injury.
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PMID:Existence and participation of xanthine oxidase in reperfusion injury of ischemic rabbit myocardium. 200 Sep 75

Using proton and phosphorus magnetic resonance spectroscopy, we evaluated the metabolic effects of preischemic administration of the N-methyl-D-aspartate antagonist dextromethorphan (50 mg/kg i.p.) during global forebrain ischemia and subsequent reperfusion in rats. Dextromethorphan-treated animals (n = 10) showed less lactate formation during ischemia than untreated animals (n = 11, p less than 0.001). During reperfusion, the lactate level in the treated group was reduced (p less than 0.05). Tissue pH declined less in the treated group during ischemia (p less than 0.01). There was no difference in the phosphocreatine/inorganic phosphate peak height ratio between groups. During ischemia, the N-acetylaspartate resonance peaks decreased in both groups. Histologic damage assessed in the hippocampal CA1 region 7 days after the ischemic insult was more severe in the untreated group (p less than 0.05). There was a significant correlation between end-ischemic tissue pH and hippocampal damage (r = -0.73, p less than 0.05). In the dextromethorphan-treated animals, 90% of the rats survived compared with 47% of the untreated animals (p less than 0.05). These results support findings in previous studies that dextromethorphan attenuates ischemic damage.
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PMID:Effects of dextromethorphan on rat brain during ischemia and reperfusion assessed by magnetic resonance spectroscopy. 200 3

The metabolic effects of R-phenylisopropyladenosine (R-PIA), an agonist of adenosine A1 receptors, were studied by in vivo 31P NMR spectroscopy before, during, and after 30 min of reversible forebrain ischemia in the rat. R-PIA had no effect on cerebral metabolism before ischemia. During a 30-min ischemia, R-PIA reduced the decrease in phosphocreatine (43 +/- 11% of the control level at the end of ischemia vs. 27 +/- 9% in the reference group) and ATP (58 +/- 12% vs. 40 +/- 23%) and the increase in inorganic phosphate (672 +/- 210% vs. 905 +/- 229%). The intracellular acidosis elicited by ischemia was also less in the treated group (pH of 6.40 +/- 0.10 vs. 6.30 +/- 0.10). Recirculation was associated with a faster recovery of PCr, ATP, Pi, and pHi to control levels in the treated group than in the reference group. It is concluded that adenosine protects against ischemic injury by mechanisms that include metabolic protection.
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PMID:Metabolic effects of R-phenylisopropyladenosine during reversible forebrain ischemia studied by in vivo 31P nuclear magnetic resonance spectroscopy. 201 53

To evaluate changes in coronary blood flow during allograft rejection, 16 beagles with cervical cardiac allografts from mongrel donors were immunosuppressed postoperatively for 7 days with cyclosporine (20 mg/kg orally) and prednisone (0.5 mg/kg orally). They were weaned from immunosuppression over 3 days and then treated with methylprednisolone (30 mg/kg/day IV), cyclosporine (20 mg/kg orally), and prednisone (0.5 mg/kg orally) for 4 days. Previous experiments with this model have suggested the utility of phosphorus 31 nuclear magnetic resonance spectroscopy (31P NMR) in the diagnosis of rejection. Therefore in 10 dogs (NMR group) bioenergetic changes during rejection were assessed using the 31P NMR index of the ratio of phosphocreatine to inorganic phosphate (PCr/Pi). To correlate coronary blood flow and graft ischemia with allograft rejection, six dogs (FLOW group) underwent placement of a magnetic flow probe on the left anterior descending coronary artery to determine mean and peak coronary flow. In both NMR and FLOW groups, grafts were evaluated by endomyocardial biopsy (grading 0 to 8 for increasing rejection), and measurement of lactate production and left ventricular end-diastolic pressure. During the initial 7 days of immunotherapy, cellular rejection was effectively suppressed, and the bioenergetic status of the grafts remained stable (day 7: PCr/Pi = 70% of baseline, biopsy score = 2.0). During weaning of immunotherapy, however, the metabolic profile of the grafts decayed (day 10: PCr/Pi = 45% of baseline, biopsy score = 5.8; p less than 0.05 vs day 0). After 4 days of augmented immunosuppression, PCr/Pi recovered to 83% of baseline; this metabolic recovery corresponded with an improvement in mean biopsy score to 3.2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Coronary blood flow does not decrease during allograft rejection in heterotopic heart transplants. 203 21

The cerebral protective effect of eptazocine, an opioid mu-antagonist-kappa-agonist, was investigated using mice and rats subjected to ischemia. 1) Decapitation or concussive head injury (20 g, 30 cm)-induced ischemia in mice: Eptazocine (3,10 mg/kg) prolonged the gasping duration or the survival time in a dose-dependent manner. 2) Ischemic brain edema induced by bilateral carotid arterial occlusion (BLCO) in rats: Administration of eptazocine just after BLCO treatment significantly prevented the incidence of ischemic seizures, lethality and an increase in cerebral water content. 3) Acute ischemic changes in cerebral energy metabolism in mice: 2-min BLCO treatment decreased the cerebral contents of phosphocreatine and ATP, and it increased the contents of AMP and lactate, resulting in a 34% decrease in energy charge potential and an increase in lactate/pyruvate ratio. Such changes were improved by eptazocine (3, 10 mg/kg) and ethylketocyclazocine (3 mg/kg), a kappa-agonist. 4) Respiratory function in mouse brain mitochondria preparations: Eptazocine increased the State 3 respiration and respiratory control index (RCI:State 3/State 4), and it prevented a decrease in RCI induced by 3-min ischemia. These results suggest that eptazocine may improve cerebral ischemic disorders through an activation and/or protection of mitochondrial energy-producing systems.
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PMID:[Protective effect of eptazocine, a novel analgesic, against cerebral ischemia in mice and rats]. 205 80

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)
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PMID:Metabolic heterogeneity in brain tissue during incomplete ischemia and reperfusion. 209 39


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