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

1. The effects of KB-2796, a new diphenylpiperazine calcium antagonist, on the mitochondrial dysfunction and energy metabolism deficits were examined in the ischemic rat brain. 2. KB-2796 (30 mg/kg, p.o.), administered 60 min prior to decapitation, improved the reduced respiratory activity of mitochondria obtained from rat brain 5 min after decapitative ischemia. 3. KB-2796 (30 mg/kg, p.o.), administered 60 min prior to ischemic insult, improved both the reductions in pyruvate and ATP and prevented increases in the lactate/pyruvate ratio induced by 30-min forebrain ischemia in rats with 4-vessel occlusion (4-VO). 4. The effect of KB-2796 on local cerebral glucose utilization (LCGU) was examined by a quantitative autoradiographic 2-[14C]deoxyglucose method in normal and 4-VO rats. 5. Postischemic LCGU measured 24 hr after reperfusion in the forebrain, in particular in the cortex, thalamus, geniculate body, hippocampus, caudate-putamen, nucleus accumbens, colliculus, and corpus callosum, was below the normal control value. 6. KB-2796 (1 mg/kg, i.v.), administered 1 min prior to the injection of 2-[14C]deoxyglucose, improved the reductions in LCGU that were produced by cerebral ischemia in the cortex, thalamus, geniculate body, caudate-putamen, nucleus accumbens and substantia nigra, but did not affect LCGU in normal rats. 7. These findings suggest that KB-2796 minimized the deficits in brain energy metabolism produced by ischemia; this agent may therefore be a valuable therapeutic drug in cerebrovascular-related disorders.
Gen Pharmacol 1993 Nov
PMID:Effects of a new diphenylpiperazine calcium antagonist, KB-2796, on cerebral ischemic neuronal damage in rats. 811 23

Chronological changes of protein kinase C (PKC) activity were measured using in vitro [3H]phorbol 12,13-dibutyrate (PDBu) autoradiography to investigate the postischemic alteration of this second messenger system in the rat brain. Transient ischemia was induced by the occlusion of the middle cerebral artery (MCA) for 90 min and such occlusion followed by various recirculation periods of up to 4 weeks. After 90 min of ischemia followed by 3 hours of recirculation, [3H]PDBu binding sites were found to be significantly decreased in the cerebral cortex and lateral segment of the caudate putamen, both supplied by the occluded MCA; thereafter, the binding sites decreased progressively in those ischemic foci. On the contrary, there was no alteration on day 1, but 3 days after ischemic insult, a significant decrease of [3H]PDBu binding sites was first detected in the ipsilateral thalamus and the substantia nigra, which both areas had not been directly affected by the original ischemic insult. This postischemic delayed phenomenon observed in the thalamus and the substantia nigra developed concurrently with 45Ca accumulation, which was detected there in our previous study. These results suggest that alteration of second messenger (PKC) pathways may be involved not only in the ischemic foci, but also in neuronal degeneration of the exo-focal remote areas in relation to the disruption of intracellular calcium homeostasis which plays a key role in the pathogenesis of postischemic neuronal damage and that marked alteration of intracellular signal transduction may precede the neuronal damage in the exo-focal postischemic brain areas.
J Neural Transm Gen Sect 1993
PMID:Alteration of protein kinase C activity in the postischemic rat brain areas using in vitro [3H]phorbol 12,13-dibutyrate autoradiography. 836 4

1. We investigated alterations in dopamine D1 receptors in the striatum and hippocampus after transient cerebral ischemia in gerbils using [3H]SCH 23390 autoradiography. 2. We also examined the effect of vinconate against the alterations in dopamine D1 receptors after transient ischemia. 3. Transient ischemia was induced for 10 min, and vinconate (100 and 300 mg/kg) was given intraperitoneally 10 min before ischemia. 4. [3H]SCH 23390 binding showed no significant alterations in the striatum and hippocampus 5 hr after ischemia, whereas severe reduction in these areas was found after 7 days of recirculation. 5. Vinconate showed no significant alterations in [3H]SCH 23390 binding in the striatum and hippocampus except for a decrease in the hippocampal CA3 sector and dentate gyrus 5 hr after ischemia. By contrast, vinconate prevented a significant reduction in [3H]SCH 23390 binding in the striatum, hippocampal CA3 sector, hilus, and dentate gyrus 7 days after ischemia. 6. Vinconate inhibited lipid peroxidation in rat brain homogenates in a concentration-related manner. 7. These results indicate that free radicals generated from abnormal dopamine metabolism may play a key role in the development of ischemic brain damage. Furthermore, they suggest that vinconate prevents ischemic brain damage by inhibiting lipid peroxidation.
Gen Pharmacol 1993 Jan
PMID:Neuroprotective effect of vinconate against postischemic alterations in binding of [3H]SCH 23390 in the gerbil brain. 848 99

1. The adenosine A1 receptor enhancer, PD 81,723, was tested for its neuroprotective activity in a Mongolian gerbil model of forebrain ischemia/reperfusion cerebral ischemia. 2. Gerbils were injected with PD 81,723 (1, 10 and 125 mg/kg i.p.) 20 min before a 5-min episode of forebrain ischemia. The extent of ischemic injury was assessed by monitoring the increases in locomotor activity and from the degree of damage to the CA1 hippocampal pyramidal cell layer after 5 days of recovery. 3. By both criteria, PD 81,723, at all three dose levels, failed to protect against ischemia/reperfusion evoked cerebral injury.
Gen Pharmacol 1995 Nov
PMID:Adenosine A1 receptor enhancer, PD 81,723, and cerebral ischemia/reperfusion injury in the gerbil. 869 Feb 43

1. Functional and antiischaemic effects of monoacetyl-vitexinrhamnoside (AVR), a flavonoid with phosphodiesterase (PDE)-inhibitory properties contained in Crataegus species (Hawthorn, Rosaceae) were studied in several in-vitro models. 2. In rabbit isolated femoral artery rings, AVR concentration-dependently reduced developed tension. Vasodilation by AVR was reduced after inhibiting EDRF formation by L-NG-nitro arginine. 3. In spontaneously-beating Langendorff-guinea pig hearts, AVR concentration-dependently enhanced heart-rate, contractility, lusitropy and coronary flow. 4. In isolated electrically-driven Langendorff-rabbit hearts, acute regional ischemia (MI) was induced by coronary artery occlusion and quantified from epicardial NADH-fluorescence photography. AVR (5 x 10(-5) mol/l) induced a slight numerical increase of left ventricular pressure and coronary flow (p > 0.05). MI was reduced (p < 0.05). 5. Monoacetyl-vitexinrhamnoside is an inodilator whose vasodilatory action may be mediated in part by EDRF in addition to PDE-inhibition. Monoacetyl-vitexinrhamnoside does possess marked antiischemic properties even in isolated hearts, suggesting an improvement of myocardial perfusion.
Gen Pharmacol 1995 Nov
PMID:Functional and antiischaemic effects of Monoacetyl-vitexinrhamnoside in different in vitro models. 869 Feb 47

Na channels open upon depolarization but then enter inactivated states from which they cannot readily reopen. After brief depolarizations, native channels enter a fast-inactivated state from which recovery at hyperpolarized potentials is rapid (< 20 ms). Prolonged depolarization induces a slow-inactivated state that requires much longer periods for recovery (> 1 s). The slow-inactivated state therefore assumes particular importance in pathological conditions, such as ischemia, in which tissues are depolarized for prolonged periods. While use-dependent block of Na channels by local anesthetics has been explained on the basis of delayed recovery of fast-inactivated Na channels, the potential contribution of slow-inactivated channels has been ignored. The principal (alpha) subunits from skeletal muscle or brain Na channels display anomalous gating behavior when expressed in Xenopus oocytes, with a high percentage entering slow-inactivated states after brief depolarizations. This enhanced slow inactivation is eliminated by coexpressing the alpha subunit with the subsidiary beta 1 subunit. We compared the lidocaine sensitivity of alpha subunits expressed in the presence and absence of the beta 1 subunit to determine the relative contributions of fast-inactivated and slow-inactivated channel block. Coexpression of beta 1 inhibited the use-dependent accumulation of lidocaine block during repetitive (1-Hz) depolarizations from -100 to -20 mV. Therefore, the time required for recovery from inactivated channel block was measured at -100 mV. Fast-inactivated (alpha + beta 1) channels were mostly unblocked within 1 s of repolarization; however, slow-inactivated (alpha alone) channels remained blocked for much longer repriming intervals (> 5 s). The affinity of the slow-inactivated state for lidocaine was estimated to be 15-25 microM, versus 24 microM for the fast-inactivated state. We conclude that slow-inactivated Na channels are blocked by lidocaine with an affinity comparable to that of fast-inactivated channels. A prominent functional consequence is potentiation of use-dependent block through a delay in repriming of lidocaine-bound slow-inactivated channels.
J Gen Physiol 1996 May
PMID:Functional consequences of lidocaine binding to slow-inactivated sodium channels. 874 Mar 77

T1. The effect of 2-chloroadenosine, an adenosine analogue, on brain ATP level and Na,K ATPase activity in ischemia and reperfusion was studied. 2. Na,K ATPase activity decreased in both ischemia and reperfusion. Although the ATP level decreased in ischemia, it increased with reperfusion (P < 0.05). 3. It is concluded that 2-chloroadenosine treatment influenced ATP production and Na,K ATPase activity in ischemia and reperfusion (P < 0.05).
Gen Pharmacol 1996 Jan
PMID:The effect of 2-chloroadenosine on the ATP level Na,K ATPase activity in experimental brain ischemia of gerbil. 874 15

1. An experimental comparative study on isolated guinea pig lungs was carried out to determine the effect of selenium added to pulmoplegic solution on ischemic lung preservation. 2. Two different types of solutions (Eurocollins in control group and Eurocollins + selenium 10(-3) M in experimental group) were infused before 3 hr of normothermic ischemia. 3. Tissue malone dialdehyde (MDA) and tissue glutathione (GSH) levels were assessed before the ischemic period, after the ischemia and at the end of reperfusion. Electron microscopic changes were also studied at the end of reperfusion to compare the cellular injury between the groups. 4. Addition of selenium before the ischemic period relatively decreased tissue MDA levels after reperfusion but did not alter tissue GSH levels.
Gen Pharmacol 1995 Dec
PMID:Effect of selenium on ischemic and reperfusion injury in isolated guinea pig lungs. 874 54

1. Streptozotocin-induced diabetic rats showed poor post-ischemic recovery in isolated working rat hearts. 2. Diabetic rats showed myocardial Na+ accumulation after ischemia, and Ca2+ level and water content elevation after reperfusion. 3. A 6-wk nifedipine treatment improved post-ischemic recovery of cardiac parameters and prevented myocardial Na+ accumulation after ischemia and myocardial Ca2+ level and water content elevation after reperfusion of diabetic rats. 4. Results suggest that nifedipine treatment improves cardiac dysfunction in the reperfused ischemic hearts of diabetic rats through normalization of the Na+-Ca2+ imbalance and water content.
Gen Pharmacol 1995 Dec
PMID:Long-term nifedipine treatment reduces calcium overload in isolated reperfused hearts of diabetic rats. 874 56

In this study, ischemia and oxidative stress-inducible gene expression in heart was examined by subtractive hybridization technique. Total RNA was isolated from ventricular muscle fragments of normal and oxidative stress-induced hearts. Poly (A)+ RNA was purified followed by the construction of a plasmid cDNA library. This was followed by the subtractive screening of oxidative stress-induced cDNA library. The positive colonies were amplified and the plasmid isolated. An aliquot was subjected to restriction cutting with Bam H1 and EcoR1; the fragments corresponding to cDNA insert were separated by electrophoresis, radiolabeled by random-primed DNA synthesis, and used as probes in standard Northern blotting experiments. An aliquot containing the plasmid from the confirmed positives was then subjected to bidirectional partial DNA sequencing (using M13 and T7/T3 alpha primers) by the chain-extension/chain termination method. These sequences were subjected to a computerized search for homologies against all sequences in the updated worldwide Gen Bank and EMBL sequence databases followed by restriction mapping and reading frame identification. Out of 24 putative positive colonies screened, one clone was matched with > 97% homology with FAT gene that has been implicated in binding or transport of long chain fatty acids. cDNA probe synthesized from this clone identified two major transcripts of 4.8 and 2.9 kb. Additional experiments were then performed where isolated perfused rat hearts were subjected to the following treatments: (1) 5 min ischemia; (2) 10 min ischemia; (3) 20 min ischemia; (4) 5 min ischemia followed by 10 min reperfusion (ischemic preconditioning); and (5) 5 min ischemia followed by 10 min reperfusion, repeated four times (4 x preconditioning). RNAs were extracted from these hearts and hybridized with the FAT cDNA probe. The results indicated the FAT gene was induced by oxidative stress, ischemic preconditioning, but not by ischemia.
 ...
PMID:Molecular cloning, sequencing and expression analysis of a fatty acid transport gene in rat heart induced by ischemic preconditioning and oxidative stress. 890 79


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