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

To elucidate the contribution of reduced activity of Na+/H+ exchange in streptozotocin-induced diabetic hearts against stunning, intracellular Na+ concentration ([Na+]i) was measured in isolated rat hearts using 23Na-MRS. The recovery of left ventricular developed pressure in hearts reperfused after 15 min global ischaemia at 37 degreesC was significantly better in diabetic ones (102.9+/-2.0% of pre-ischemic level, mean+/-s.e., n=6; P<0.05), and non-diabetic ones pre-treated with potent Na+/H+ exchange inhibitor, EIPA (1 mu mol/l; 93.8+/-2.3%, n=5; *P<0.05) than non-treated, non-diabetic hearts (75.1+/-2.5%, n=8). When diabetic hearts were pre-treated with EIPA, the recovery (101.2+/-2.6%, n=5) was identical to that of non-treated, diabetic hearts. [Na+]i in non-diabetic hearts increased to 329.1+/-8.1% of pre-ischemic level during 15 min ischemia, whereas the increase in [Na+]i in diabetic hearts significantly suppressed to 199.8+/-10.3% (P<0.001). EIPA attenuated the increase of [Na+]i during ischemia to 189.1+/-9.0% in non-diabetic hearts ( P<0.001) and to 155.3+/-4.6% in diabetic hearts (P<0.05). Thus, the EIPA-dependent Na+ accumulation during ischemia, i.e. Na+ influx probably mostly via Na+/H+ exchange was smaller in diabetic hearts by 69.7% compared with that in non-diabetic hearts. These results indicate that the cardiac protection against stunning in streptozotocin-induced diabetic hearts is mediated by the attenuation of Na+ accumulation during ischemia, which is caused by the reduced activity in Na+/H+ exchanger.
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PMID:Alteration of intracellular Na+ during ischemia in diabetic rat hearts: the role of reduced activity in Na+/H+ exchange against stunning. 951 28

Putative changes of metabolite T2 relaxation times were investigated before and after a 20-min period of global ischemia in rat brain in vivo (n = 10) using localized proton MRS at different echo times (2.35 T). Neither absolute T2 relaxation times (TE = 20-270 ms) nor time courses of T2-weighted metabolite signals (TE = 135 ms) revealed statistically significant changes during the occlusion or early reperfusion relative to pre-ischemic baseline. These findings are in line with reports of relaxation changes at much later stages and further demonstrate that altered T2 relaxation is not a confounding factor in diffusion-weighted long-TE proton MRS during early ischemic events.
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PMID:Proton T2 relaxation of cerebral metabolites during transient global ischemia in rat brain. 954 28

Cerebral apparent diffusion coefficients (ADCs) were determined in nine newborn piglets before and for 48 h after transient hypoxia-ischemia. Phosphorus MRS revealed severely reduced cerebral energy metabolism during the insult and an apparently complete recovery 2 h after resuscitation commenced. At this time, mean ADC over the imaging slice (ADCglobal) was 0.88 (0.04) x 10(-9) m2 x s(-1) (mean (SD)), which was close to the baseline value of 0.92 (0.4) x 10(-9) m2 x s(-1). In seven of the animals, a "secondary" failure of energy metabolism then evolved, accompanied by a decline in ADCglobal to 0.64 (0.17) x 10(-9) m2 x s(-1) at 46 h postresuscitation (P < 0.001 versus baseline). For these seven animals, ADCglobal correlated linearly with the concentration ratio [phosphocreatine (PCr)]/[inorganic phosphate (Pi)] (0.94 < r < 0.99; P < 0.001). A nonlinear relationship was demonstrated between ADCglobal and the concentration ratio [nucleotide triphosphate (NTP)]/[Pi + PCr + 3 NTP]. The ADC reduction commenced in the parasagittal cortex before spreading in a characteristic pattern throughout the brain. ADC seems to be closely related to cerebral energy status and shows considerable potential for the assessment of hypoxic-ischemic injury in the newborn brain.
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PMID:Temporal and anatomical variations of brain water apparent diffusion coefficient in perinatal cerebral hypoxic-ischemic injury: relationships to cerebral energy metabolism. 962 15

A 63-year-old man developed a severe left frontal headache followed by an acute change of mentality 6 days later. Magnetic resonance imaging revealed bilateral thalamic ischemia. Angiography confirmed the occlusion of deep cerebral veins. Proton magnetic resonance spectroscopy (1H-MRS) of the thalami showed normal N-acetylaspartate (NAA) peak and the presence of lactate peak, indicating a relatively preserved neuronal viability. The patient improved during the follow-up period, and returned to work 45 days after the onset of the disease. With 1H-MRS, prognosis following venous infarctions may be feasible.
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PMID:Proton magnetic resonance spectroscopy in deep cerebral venous thrombosis. 963

In this prospective study proton magnetic resonance spectroscopy (1H MRS) was used to test the hypothesis that lactate can be detected later than 1 mo after birth in the brains of infants who display severe neurodevelopmental impairment 1 y after transient perinatal hypoxia-ischemia. Data were obtained from three groups of infants: 1) eight infants suffering birth asphyxia followed by perinatal encephalopathy and abnormal neurodevelopmental outcome at 1 y of age (defined as major neurologic impairment, Griffiths quotient <85%, and low optimality score); 2) 10 infants with signs of perinatal hypoxia-ischemia but normal neurodevelopmental outcome at 1 y; and 3) six control infants with uneventful perinatal courses and normal neurodevelopment at 1 y. Between one and four examinations (median 1) were performed at median (range) 11 (4-68) wk after birth, and the cerebral concentration ratio of lactate to creatine plus phosphocreatine (Cr) calculated from each spectrum. Lactate was detected later than the 1st mo after birth in seven of eight infants with abnormal neurodevelopmental outcome [maximum detected lactate/Cr was median (range) 0.44 (0.24-0.67)]. No lactate was detected later than the 1st mo after birth in infants with normal neurodevelopmental outcome, nor in five of six control subjects, although a small amount of lactate was detected in one control infant (lactate/Cr=0.04). These results suggest that the pathologic postasphyxial process, indicated by persistent cerebral lactate, may not be confined to the period immediately after injury.
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PMID:Persistent increases in cerebral lactate concentration after birth asphyxia. 972 5

Brain N-acetylaspartate (NAA) can be quantified by in vivo proton magnetic resonance spectroscopy (1H-MRS) and is used in clinical settings as a marker of neuronal density. It is, however, uncertain whether the change in brain NAA content in acute stroke is reliably measured by 1H-MRS and how NAA is distributed within the ischemic area. Rats were exposed to middle cerebral artery occlusion. Preischemic values of [NAA] in striatum were 11 mmol/L by 1H-MRS and 8 mmol/kg by HPLC. The methods showed a comparable reduction during the 8 hours of ischemia. The interstitial level of [NAA] ([NAA]e) was determined by microdialysis using [3H]NAA to assess in vivo recovery. After induction of ischemia, [NAA]e increased linearly from 70 micromol/L to a peak level of 2 mmol/L after 2 to 3 hours before declining to 0.7 mmol/L at 7 hours. For comparison, [NAA]e was measured in striatum during global ischemia, revealing that [NAA]e increased linearly to 4 mmol/L after 3 hours and this level was maintained for the next 4 h. From the change in in vivo recovery of the interstitial space volume marker [14C]mannitol, the relative amount of NAA distributed in the interstitial space was calculated to be 0.2% of the total brain NAA during normal conditions and only 2 to 6% during ischemia. It was concluded that the majority of brain NAA is intracellularly located during ischemia despite large increases of interstitial [NAA]. Thus, MR quantification of NAA during acute ischemia reflects primarily changes in intracellular levels of NAA.
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PMID:N-Acetylaspartate distribution in rat brain striatum during acute brain ischemia. 1002 72

We have developed a noninvasive detection method for expression of viral-mediated gene transfer. A recombinant adenovirus was constructed by using the gene for arginine kinase (AK), which is the invertebrate correlate to the vertebrate ATP-buffering enzyme, creatine kinase. Gene expression was noninvasively monitored using (31)P-magnetic resonance spectroscopy ((31)P-MRS). The product of the AK enzyme, phosphoarginine (PArg), served as an MRS-visible reporter of AK expression. The recombinant adenovirus coding for arginine kinase (rAdCMVAK) was injected into the right hindlimbs of neonatal mice. Two weeks after injection of rAdCMVAK, a unique (31)P-MRS resonance was observed. It was observable in all rAdCMVAK injected hindlimbs and was not present in the contralateral control or the vehicle injected limb. PArg and phosphocreatine (PCr) concentrations were calculated to be 11.6 +/- 0.90 and 13.6 +/- 1.1 mM respectively in rAdCMVAK injected limbs. AK activity was demonstrated in vivo by monitoring the decreases in PArg and ATP resonances during prolonged ischemia. After 1 h of ischemia intracellular pH was 6.73 +/- 0.06, PCr/ATP was decreased by 77 +/- 8%, whereas PArg/ATP was decreased by 50 +/- 15% of basal levels. PArg and PCr returned to basal levels within 5 min of the restoration of blood flow. AK activity persisted for at least 8 mo after injection, indicating that adenoviral-mediated gene transfer can produce stable expression for long periods of time. Therefore, the cDNA encoding AK provides a useful reporter gene that allows noninvasive and repeated monitoring of gene expression after viral mediated gene transfer to muscle.
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PMID:Noninvasive measurement of gene expression in skeletal muscle. 1080 78

Adenosine released during cardiac ischemia exerts a potent, protective effect in the heart via activation of A(1) or A(3) receptors. However, the interaction between the two cardioprotective adenosine receptors and the question of which receptor is the more important anti-ischemic receptor remain largely unexplored. The objective of this study was to test the hypothesis that activation of both receptors exerted a cardioprotective effect that was significantly greater than activation of either receptor individually. This was accomplished by using a novel design in which new binary conjugates of adenosine A(1) and A(3) receptor agonists were synthesized and tested in a novel cardiac myocyte model of adenosine-elicited cardioprotection. Binary drugs having mixed selectivity for both A(1) and A(3) receptors were created through the covalent linking of functionalized congeners of adenosine agonists, each being selective for either the A(1) or A(3) receptor subtype. MRS 1740 and MRS 1741, thiourea-linked, regioisomers of a binary conjugate, were highly potent and selective in radioligand binding assays for A(1) and A(3) receptors (K(i) values of 0.7-3.5 nm) versus A(2A) receptors. The myocyte models utilized cultured chick embryo cells, either ventricular cells expressing native adenosine A(1) and A(3) receptors, or engineered atrial cells, in which either human A(3) receptors alone or both human A(1) and A(3) receptors were expressed. The binary agonist MRS 1741 coactivated A(1) and A(3) receptors simultaneously, with full cardioprotection (EC(50) approximately 0.1 nm) dependent on expression of both receptors. Thus, co-activation of both adenosine A(1) and A(3) receptors by the binary A(1)/A(3) agonists represents a novel general cardioprotective approach for the treatment of myocardial ischemia.
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PMID:A novel pharmacological approach to treating cardiac ischemia. Binary conjugates of A1 and A3 adenosine receptor agonists. 1088 76

Adenosine-enhanced ischemic preconditioning (APC) extends the cardioprotection of ischemic preconditioning (IPC) by both significantly decreasing myocardial infarct size and significantly enhancing postischemic functional recovery. In this study, the role of adenosine receptors during ischemia-reperfusion was determined. Rabbit hearts (n = 92) were used for Langendorff perfusion. Control hearts were perfused for 180 min, global ischemia hearts received 30-min ischemia and 120-min reperfusion, and IPC hearts received 5-min ischemia and 5-min reperfusion before ischemia. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine receptor (A(1), A(2), and A(3)) antagonists were used with APC before ischemia and/or during reperfusion. GR-69019X (A(1)/A(3)) and MRS-1191/MRS-1220 (A(3)) significantly increased infarct size in APC hearts when administered before ischemia and significantly decreased functional recovery when administered during both ischemia and reperfusion (P < 0.05 vs. APC). DPCPX (A(1)) administered either before ischemia and/or during reperfusion had no effect on APC cardioprotection. APC-enhanced infarct size reduction is modulated by adenosine receptors primarily during ischemia, whereas APC-enhanced postischemic functional recovery is modulated by adenosine receptors during both ischemia and reperfusion.
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PMID:Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion. 1115 56

Global brain ischemia provoked by transient occlusion of the carotid arteries (2VO) in gerbils results in a severe loss of neurons in the hippocampal CA1 region. We measured the concentration of the neuron specific N-acetyl-aspartate, [NAA], in the gerbil dorsal hippocampus by proton MR spectroscopy (1H-MRS) in situ, and HPLC, 4 days after global ischemia. The [NAA] was correlated with graded hippocampus damage scoring and stereologically determined neuronal density. A basal hippocampal [NAA] of 8.37+/-0.10 and 9.81+/-0.44 mmol/l were found from HPLC and 1H-MRS, respectively. HPLC measurements of [NAA] obtained from hippocampus 4 days after 2VO showed a 20% reduction in the [NAA] following 4 min of ischemia (P<0.001). 1H-MRS measurements on gerbils subjected to 4 or 8 min of ischemia showed a similar 24% decline in the [NAA] (P<0.05). Thus, there was correlation between the HPLC and 1H-MRS determined NAA decline. There was also a significant correlation between 1H-MRS [NAA] and the corresponding reduction in CA1 neuronal density (P<0.004). In summary our findings show that single voxel 1H-MRS can be used as a supplement to histological evaluation of neuronal injury in studies after global brain ischemia. Accordingly, volume selective spectroscopy has a potential for assessment of neuroprotective therapeutic compounds/strategies with respect to neuronal rescue for delayed ischemic brain damage.
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PMID:Evaluation of CA1 damage using single-voxel 1H-MRS and un-biased stereology: Can non-invasive measures of N-acetyl-asparate following global ischemia be used as a reliable measure of neuronal damage? 1117 61


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