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

Recent evidence suggests that muscarinic receptors play a role in the hippocampal hypersensitivity to imposed ischemia following mild traumatic brain injury (TBI). In rat hippocampal tissue, carbachol-stimulated inositol phosphate production was found to be enhanced by mild TBI, at 1 h post injury. This finding suggests that mild TBI may result in enhanced coupling between muscarinic receptors and phosphoinositide hydrolysis, which may contribute to post-traumatic hippocampal vulnerability to secondary ischemia.
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PMID:Mild traumatic brain injury enhances muscarinic receptor-linked inositol phosphate production in rat hippocampus. 145 Sep 57

31P NMR spectroscopy was used to assess the cerebral ischemia status in rats by measuring the relative levels of phosphate metabolites. Partial cerebral ischemia was induced in 49 rats by reversible occlusion of the carotid arteries. Rats were intubated and mechanically ventilated on a hypoxic gas mixture. Physiological parameters such as temperature and arterial pressure were strictly controlled during the experiments. 31P spectra were acquired at 7 T during basal observation, for 15-20 min after the induction of ischemia, and for 1 hr after reperfusion. Depletion and increase in PCr and Pi levels, respectively, were already observable in the collected spectra within few minutes after the onset of ischemia. No appreciable changes were found in the ATP levels.
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PMID:Partial cerebral ischemia assessed by "in vivo" 31P NMR spectroscopy in rats. 146 Oct 71

Myocardial ischemia has traditionally been characterized as an imbalance between energy supply and demand. In the initial seconds after a sudden reduction of coronary blood flow, myocardial energy demand most certainly exceeds the reduced energy supply. This temporary mismatch, however, is an inherently unstable condition because regional contractile dysfunction ensues. The mechanisms responsible for the rapid reduction in contractile function of the acutely ischemic myocardium are still poorly understood. If some residual blood flow exists, a state of "perfusion-contraction matching" can be maintained without the development of irreversible damage. The metabolic status of such hypoperfused myocardium improves as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. The hypoperfused myocardium can respond to inotropic stimulation by dobutamine with increased function. The recruitment of an inotropic reserve implies increased energy utilization. In fact, the partially normalized lactate production is again increased, and creatine phosphate is decreased again. Apparently, the inotropic challenge once again precipitates a supply-demand imbalance which had been at least partially corrected by the ischemia-induced decrease of regional contractile function. A situation of chronic contractile failure in viable myocardium which normalizes upon reperfusion has been termed myocardial "Hibernation". Myocardial "Stunning" is characterized by a reversible post-ischemic contractile dysfunction despite full restoration of blood flow. The underlying mechanisms are not clear in detail. An inadequate energy supply and an impaired sympathetic neurotransmission have been excluded. Potential mechanisms, which are not mutually exclusive, may include (1) damage of membranes and enzymes by free radicals, (2) an increase in free cytosolic calcium during ischemia and reperfusion, and (3) a decrease of the calcium sensitivity of the myofibrils. The equally pronounced increases in regional contractility in normal and "stunned" myocardium during intracoronary calcium infusion, postextrasystolic potentiation and the infusion of the calcium-sensitizing agent AR-L-57, however, suggest an unchanged calcium sensitivity of reperfused myocardium. Interventions to reduce free radical formation or to increase their elimination attenuate myocardial stunning. Likewise, pretreatment with calcium antagonists before ischemia attenuates myocardial stunning. This effect is probably related to an attenuated myocardial calcium overload during early ischemia. The potential benefit from calcium antagonists when given after established reperfusion remains controversial.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Hibernation, stunning, ischemic preconditioning--new paradigms in coronary disease?]. 147 97

Using 31P nuclear magnetic resonance, the following parameters were determined in the resting musculus erector spinae of five patients suffering from chronic low back pain, five patients with fibromyalgia, and five healthy controls: Inorganic phosphate (Pi), phosphocreatine (PCr), ATP gamma, ATP alpha, ATP beta. The intracellular pH was derived from the chemical shift of Pi referenced to the PCr resonance. In addition, the Pi-Index was calculated according to the formula: Pi/(Pi + PCr). We discovered a tendency towards a shift of the Pi resonance in the alcalic direction, which was the larger, the stronger muscle spasm was found on palpation. The pH showed the most reliable relationship to the clinical status of muscle spasm. The surprising finding that there is no acidification within the spasmed muscle indicates that generalized hypoxia does not exist in this tissue. This has already been shown with PO2 measurements. An intracellular acidification is only recorded during maximal isometric contraction. Thus, ischemia cannot be responsible for pain experienced during muscle spasm.
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PMID:[Recording muscle spasm in the musculus erector spinae using in vivo 31P magnetic resonance spectroscopy in patients with chronic lumbalgia and generalized tendomyopathies]. 147 7

We investigated the effect of reversible ischemia, leading to persistent contractile dysfunction (stunning), on myocardial energy metabolism. The balance of energy metabolism is expressed by the phosphorylation state of cytosolic nucleotides. This variable cannot be measured directly because of nucleotide compartmentation, but in the isolated heart it can be estimated by the release of purine catabolites. We have previously shown that increased energy consumption or impaired energy production cause purine release to increase, while primary reduction in energy consumption has the opposite effect. Isolated working rat hearts were reperfused after 10 min of global ischemia, measuring hemodynamic variables, tissue high energy phosphate compounds and purine release. In post-ischemic recovery, aortic flow and minute work decreased to 82 +/- 3% and 77 +/- 4% of control, adenine nucleotide pool was reduced by 4.6 mumol/g dry wt, phosphocreatine to creatine ratio increased significantly and purine release decreased to 42 +/- 6% (P < 0.01). The rate of purine salvage, as evaluated by the incorporation of exogenous 3H-adenosine and 14C-hypoxanthine into tissue nucleotides, was much lower than net purine release, and was unchanged after ischemia and reperfusion. The adenine nucleotide pool could be depleted to the same extent as in the stunned myocardium by prolonged (60 min) aerobic perfusion. In this group the hemodynamic variables were unchanged and purine release averaged 87 +/- 9% of control (P = NS). In other experiments prolonged perfusion was combined with preload reduction in order to decrease energy demand. This protocol reproduced the effects of ischemia-reperfusion: aortic flow and minute work averaged 79 +/- 4% and 73 +/- 9% of control, adenine nucleotide depletion was 4.4 mumol/g dry wt and purine release decreased to 38 +/- 5% (P < 0.01). Our findings support the view that stunning is not due to adenine nucleotide depletion or to impairment in energy production, which would cause purine release to increase, but rather to primary reduction in energy utilization.
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PMID:Energy metabolism in myocardial stunning. 147 19

Depletion of high-energy phosphates, accumulation of inorganic phosphate and intracellular acidosis have each been proposed as important events in the transition from reversible to irreversible ischemic injury. To assess whether each variable is predictive of functional recovery on reperfusion, these were measured in the isolated isovolumic rat heart using 31P NMR. Perfused hearts were subjected to either 10, 12 or 40 min of normothermic ischemia followed by 40 min of reperfusion. Hearts were then freeze-clamped for further analysis of phosphate metabolites by NMR and ion chromatography. High-energy phosphates, Pi, phosphomonoesters and pH were measured by 31P NMR spectroscopy at 2 minute intervals. Heart rate and developed pressure were monitored simultaneously. All hearts undergoing 10 min of ischemia and 40% of hearts subjected to 12 min of ischemia demonstrated good functional recovery. The remainder of hearts ischemic for 12 min went into contracture on reperfusion with little return of function. Hearts subject to 40 min of ischemia went into ischemic contracture and showed no recovery on reperfusion. Intracellular pH, [ATP], and [Pi] measured prior to reperfusion did not predict the extent of recovery. However, phosphomonoesters were detected prior to reperfusion in all hearts that did not recover well, but were not observed in hearts that showed good mechanical recovery. Analysis of tissue extracts by 31P NMR and ion chromatography indicated that the most prominent components of the phosphomonoesters were glucose 6-phosphate, alpha-glycerol phosphate and AMP. In conclusion, of the various phosphorus metabolites that can be measured by 31P NMR, only one group, the phosphomonoesters, was predictive of functional recovery.
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PMID:Predicting functional recovery from ischemia in the rat myocardium. 148 87

The effect of hypoxia on the incorporation of [14C]serine into serine glycerophospholipids was investigated in rat brain cortex. Brain slices were incubated, in the presence of the labeled precursor, in Krebs-Henseleit Ringer bicarbonate or Krebs Ringer phosphate, and hypoxia was induced by bubbling nitrogen in the medium. The lowering of oxygen caused an increase of the incorporation of the base into phosphatidylserine in slices incubated in both media, although the effect was greater in Krebs Ringer phosphate. Such an effect was also observed in the homogenate subjected to N2-treatment, with an increase in the incorporation similar to that obtained in slices incubated in Krebs-Henseleit Ringer bicarbonate. Phosphatidylserine is synthesized in mammalian tissues by a "base-exchange" enzyme, strictly Ca2+ dependent, and, moreover, is necessary for protein kinase C activity. We postulate that the increased synthesis of phosphatidylserine might affect signal transduction mechanisms and participate in the modification of lipid metabolism observed in hypoxia and/or ischemia.
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PMID:Serine incorporation into phosphatidylserine in hypoxic rat brain cortex. 149 81

We used the isolated perfused working rat heart to investigate the effects of transient hypocalcemic reperfusion after cardioplegic arrest with the St. Thomas' Hospital cardioplegic solution and 25 minutes of global normothermic (37 degrees C) ischemia. Hearts were reperfused (Langendorff mode) transiently (20 minutes) with solutions containing various concentrations of calcium; this was followed by 30 minutes of reperfusion with standard (1.4 mmol/L, the physiologic concentration) calcium buffer (10 minutes in the Langendorff mode and 20 minutes in the working mode). Recovery of cardiac output in control hearts (calcium concentration 1.4 mmol/L throughout) was 51.7% +/- 4.6%; in hearts transiently reperfused with hypocalcemic buffer (0.25, 0.5, 0.75, or 1.0 mmol/L) the recoveries of cardiac output were 49.3% +/- 6.4%, 52.2% +/- 7.2%, 58.7% +/- 3.2%, and 47.2 +/- 4.7%, respectively (all not significant), whereas recovery was only 14.7% +/- 2.8% (p less than 0.05) in hearts transiently reperfused with calcium 0.1 mmol/L. Creatine kinase leakage was significantly (p less than 0.05) greater in the group reperfused with calcium 0.1 mmol/L, but it did not vary significantly between the other groups. Tissue high-energy phosphate content was similar and in the normal range in all groups except for the group reperfused with calcium 0.1 mmol/L. In further experiments, the duration of hypocalcemic (0.5 mmol/L) reperfusion was varied (0, 5, 10, 15, 20, or 30 minutes). No significant differences in recovery of cardiac output were observed (58.2% +/- 5.0%, 52.3% +/- 5.7%, 52.0% +/- 8.2%, 61.2% +/- 5.0%, 62.2% +/- 4.3%, and 66.2% +/- 3.2%, respectively). In additional studies, the standard calcium concentration (1.4 mmol/L) used before and after ischemia was replaced by hypercalcemic solution (2.5 mmol/L). Despite this, transient (10 minutes) hypocalcemic (0.5 mmol/L) reperfusion did not improve recovery. Finally, studies were undertaken with a longer duration of ischemia (40 minutes), and although recovery of cardiac output in the hypocalcemic group (0.5 mmol/L for 10 minutes) tended to be higher than in the control group (29.7% +/- 4.8% versus 18.5% +/- 4.9%, respectively), statistical significance was not achieved. We conclude that in these studies transient hypocalcemic reperfusion did not afford any additional protection over and above that afforded by cardioplegia alone.
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PMID:Transient hypocalcemic reperfusion does not improve postischemic recovery in the rat heart after preservation with St. Thomas' Hospital cardioplegic solution. 149 96

U74006F is a new 21-amino steroid (lazaroid) that prevents lipid peroxidation without glucocorticoid or mineralocorticoid side effects. Reperfusion injury has been reduced by the addition of various free radical scavengers and antiperoxidants to the reperfusate. To assess the effect of U74006F on reperfusion of donor hearts subjected to prolonged hypothermic ischemia, 21 isolated canine hearts were divided into three groups: control (group 1), drug (2 mg/kg) injected into the oxygenated blood perfusate immediately before 4 hours of preservation (group 2), and drug (2 mg/kg) injected 1 hour before heart isolation and again 15 minutes before reperfusion (group 3). After control left ventricular function studies (with an intraventricular balloon) and biopsy for high-energy phosphates and dry/wet ratios, the hearts were arrested with cold cardioplegia and cooled for 4 hours then reperfused for 3 hours. Left ventricular work was calculated by systolic and diastolic pressure curves, which showed a better return of function in group 3 hearts (1625, 2150, and 3493 mm Hg/ml in groups 1, 2, and 3, respectively, at 180 minutes of reperfusion; p = 0.02). This was likely the result of improved diastolic compliance in group 3. Dry/wet ratios showed increased tissue edema in all hearts at the end of reperfusion. Although high-energy phosphate concentrations were not different between groups, adenosine was best preserved in group 3 (p = 0.03), suggesting reduced washout of this precursor. In conclusion, administration of U74006F before preservation and reperfusion may be useful for donor heart protection.
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PMID:Improved donor myocardial recovery with a new lazaroid lipid antiperoxidant in the isolated canine heart. 149 26

Preservation of the liver involves a period of cold (0 degrees to 4 degrees C) ischemia; the longer the ischemic period, the greater the injury to the liver. The mechanisms for cold-induced ischemic injury are not known, but it is clear that after preservation the liver has a reduced capacity to regenerate high-energy phosphate compounds (ATP). One cause for the delayed rate of ATP synthesis could be injury to the mitochondria. The effects of long-term (more than 24 hr) preservation on liver mitochondrial function have not been previously studied. In this study, rat livers were preserved in University of Wisconsin solution at 4 degrees C for up to 96 hr. After preservation, mitochondrial respiratory function was assayed in a homogenate and in isolated mitochondria. We saw a progressive increase in oligomycin-sensitive respiration with time of preservation (from 1.2 +/- 0.09 mumol.min-1.gm tissue-1 at 0 hr to 3.8 +/- 0.2 mumol.min-1.gm tissue-1 after 96 hr). The increase after 24-hr preservation (2.1 +/- 0.2 mumol.min-1.gm tissue-1) was also significantly greater than 0 time values (p less than 0.05). No decrease was found in uncoupler-stimulated respiration for up to 48 hr of preservation; only a small decrease was seen after 72 hr of preservation (about 30%). The cause of the increase in oligomycin-sensitive respiration appeared to be related to free fatty acids (or another uncoupling factor) generated during preservation. This was suggested from the fact that bovine serum albumin prevented the increase in oligomycin-sensitive respiration after all periods of preservation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Loss of mitochondrial respiratory function and its suppression during cold ischemic preservation of rat livers with University of Wisconsin solution. 150 19


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