Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using microdialysis, extracellular noradrenaline (NA) levels in the rat cerebral cortex were studied under isoflurane/N2O anaesthesia before, during and for 6 hours following 10 min of forebrain ischemia in a 2-vessel occlusion model. A microdialysis probe was introduced into the parietal cortex and dorsal hippocampus in anaesthetized rats and continuously perfused with Krebs-Ringer-bicarbonate buffer with or without the NA uptake inhibitor desipramine (DMI, 5 microM). Twenty min fractions were collected and the extracellular NA levels were measured in the dialysates using HPLC with electrochemical detection. The basal NA concentration in the dialysate was 10.5 +/- 1.8 (mean +/- SEM) pg/20 min fraction and increased to 39.3 +/- 4.8 pg/20 min fraction after local administration of DMI. During ischemia, NA increased to 38 times the basal level without DMI, and 6 times with DMI included during two hours' perfusion prior to ischemia. After recirculation NA levels returned to, or even transiently decreased below, preischemic values. With DMI present in the dialysis buffer, administration of idazoxan immediately following ischemia delayed the return to preischemic NA levels in the recirculation phase. In the absence of DMI, no effect of idazoxan on postischemic levels of NA was found. Local administration of DMI increases basal extracellular NA levels and reduces the ischemia-induced NA release. The latter effect may be a due to inhibition of the NA uptake system working in a reversed mode, or as a result of decreased synthesis of NA due to activation of presynaptic alpha 2-receptors by the increased synaptic NA levels. Postischemic treatment with the alpha 2-adrenoceptor antagonist idazoxan in combination with DMI prolongs the period of elevated extracellular NA levels, which may be of importance for the protective properties of idazoxan against ischemic cell injury.
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PMID:Extracellular brain cortical levels of noradrenaline in ischemia: effects of desipramine and postischemic administration of idazoxan. 168 52

Isolated Langendorff-perfused rat hearts set up to allow measurement of mechanical myocardial function (according to Bardenheuer and Schrader) were subjected to 60 min of global ischemia (gI). The hearts were perfused with a modified Krebs-Henseleit solution (KHS; control group) or KHS with desipramine (DMI group) 100 nM. Extracellular concentrations of K+, Na+, and H+ were determined using ion-selective membrane polyvinyl chloride (PVC) minielectrodes. The noradrenaline (NA) release was estimated by analyzing the NA overflow during a 10-min reperfusion period, using high pressure liquid chromatography (HPLC). Control hearts and DMI-treated hearts showed no differences in mechanical performance prior to gI. In control hearts, the onset of gI resulted in a rapid triphasic [K+]e accumulation (an increase from 4.25 +/- 0.25 to 8.76 +/- 0.37 mmol/L during the first 3.5 min, a decrease to 8.06 +/- 0.34 mmol/L until the seventh min, and a further increase to 33.0 +/- 2.42 mmol/L at 60 min), a rapid increase in [H+]e (45.9 +/- 2.3 to 1314.5 +/- 214 nmol/L during 23 min), and a slight initial increase of [Na+]e (138.8 +/- 0.4 to 141.9 +/- 0.8 mmol/L within 8 min) followed by a long-lasting decrease (119.1 +/- 4.5 mmol/L at 60 min). Treatment with DMI had only slight effects on ionic redistribution during the course of ischemia. The [K-]e and [H-]e accumulation tended to be diminished, whereas [Na-]e values were slightly higher in the course of gI compared to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of desipramine on ischemia-induced changes in extracellular K+, Na+, and H+ concentrations and noradrenaline release in the isolated rat heart during global ischemia. 246 40

Acute ischemia has been reported to impair sympathetic outflow distal to the ischemic area in various organs, whereas relatively little is known about this phenomenon in skeletal muscle. We examined how acute ischemia affects norepinephrine (NE) release at skeletal muscle sympathetic nerve endings. We implanted a dialysis probe into the adductor muscle in anesthetized rabbits and measured dialysate NE levels as an index of skeletal muscle interstitial NE levels. Regional ischemia was introduced by microsphere injection and ligation of the common iliac artery. The time courses of dialysate NE levels were examined during prolonged ischemia. Ischemia induced a decrease in the dialysate NE level (from 19+/-4 to 2.0+/-0 pg/ml, mean+/-S.E.), and then a progressive increase in the dialysate NE level. The increment in the dialysate NE level was examined with local administration of desipramine (DMI, a membrane NE transport inhibitor), omega-conotoxin GVIA (CTX, an N-type Ca(2+) channel blocker), or TMB-8 (an intracellular Ca(2+) antagonist). At 4h ischemia, the increment in the dialysate NE level (vehicle group, 143+/-30 pg/ml) was suppressed by TMB-8 (25+/-5 pg/ml) but not by DMI (128+/-10 pg/ml) or CTX (122+/-18 pg/ml). At 6h ischemia, the increment in the dialysate NE level was not suppressed by the pretreatment. Ischemia induced biphasic responses in the skeletal muscle. Initial reduction of NE release may be mediated by an impairment of axonal conduction and/or NE release function, while in the later phase, the skeletal muscle ischemia-induced NE release was partly attributable to exocytosis via intracellular Ca(2+) overload rather than opening of calcium channels or carrier mediated outward transport of NE.
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PMID:Effect of sustained limb ischemia on norepinephrine release from skeletal muscle sympathetic nerve endings. 1663 86