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)

Cerebrovascular carbon dioxide (CO2) reactivity is an important hemodynamic index in cerebrovascular disease. In the present study T2*-weighted magnetic resonance image (T2* WI) was evaluated as a non-invasive method to investigate changes in CO2 reactivity. Fourteen rats were subjected to permanent or, 30 and 90 min of temporary middle cerebral artery occlusion. A series of T2* WIs and diffusion-weighted magnetic resonance images (DWI) was performed hourly under normo- and hypercapnic conditions. Triphenyltetrazolium chloride (TTC) staining of brain sections was obtained at the end of experiment to evaluate ischemic damage. During ischemia, a 4-6% signal increase upon hypercapnia was observed on T2* WI in the non-ischemic hemisphere, while no such reactivity was seen in the putamen and cortex ipsilateral to the MCA occlusion. After reperfusion, CO2 reactivity recovered in the putamen and cortex in the 30 min ischemia group and in the cortex alone of the 90 min ischemia groups. The areas with irreversible CO2 reactivity dysfunction coincidentally revealed no recovery on DWI and lack of TTC staining. The results indicate that T2* WI can be used to monitor changes in CO2 reactivity after various ischemic insults that may indicate tissue viability.
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PMID:T2*-weighted magnetic resonance imaging of cerebrovascular reactivity in rat reversible focal cerebral ischemia. 902 80

619C89 is a use-dependent Na+ channel antagonist that decreases the release of glutamate during ischemia. The efficacy of this drug in reducing infarction volume 72 h after occlusion of the middle cerebral artery (MCA) for 2 h in rats (n = 93) was determined by analysis of TTC-stained coronal section of the brain. Doses of 10, 20, 30 and 50 mg/kg of study drug given i.v. prior to MCA occlusion significantly (P < 0.05-0.01) reduced infarction volume in cortex compared to vehicle controls. Only the 50 mg/kg dose reduced infarction volume in the striatum (P < 0.05). Administration of 50 mg/kg of 619C89 30 and 60 min after the onset of ischemia reduced cortical infarction volume (P < 0.05), but there was no effect when the drug was given 5 min after reperfusion. No post-treatment regimen reduced striatal infarction volume. These results confirm the neuroprotective effects of 619C89 in temporary focal ischemia.
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PMID:Neuroprotective effects of the glutamate release inhibitor 619C89 in temporary middle cerebral artery occlusion. 907 Jun 37

This study tests the hypothesis that increased levels of plasma lipids can accelerate accumulation of myocardial triacylglycerols in post-ischemic but viable myocardium. Two groups of dogs underwent 90 min of left anterior descending coronary artery (LAD) occlusion followed by 240 min of reperfusion. The first group of saline-treated dogs (n = 7) had physiological levels of plasma lipids during reperfusion: a second group treated with Liposyn and heparin (n = 5) experienced increased plasma lipids during reperfusion. The transmural content of triacylglycerols was determined during ischemia and reperfusion using 1H NMR one-dimensional chemical shift imaging (1D CSI), and at the end of reperfusion using Oil Red-O staining and chemical assay. TTC staining was used to identify the extent of irreversibly injured myocardium. Subepicardial and plasma triacylglycerol content, measured both by 1D CSI and chemically, did not change during reperfusion in saline-treated dogs. Infusing dogs with Liposyn and heparin for 90 min during reperfusion transiently elevated their plasma triacylglycerols, which returned to normal levels following Liposyn wash-out. During Liposyn wash-out, myocardial triacylglycerols measured by 1D CSI preferentially increased in the subepicardium of area-at-risk myocardium (P < 0.05). Triacylglycerol content, measured chemically, also increased in area-at-risk compared to non-ischemic subepicardium (P < 0.001). Significant endocardial damage occurred in both groups, but elevated levels of plasma lipids did not increase the size of the area-at-risk. Therefore, elevated plasma lipids caused a preferential accumulation of triacylglycerols in area-at-risk myocardium during reperfusion without exacerbating irreversible ischemic injury. These results are consistent with either inhibited fatty acid oxidation or mis-matched fatty acid extraction and oxidation in area-at-risk myocardium.
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PMID:1H NMR measurement of triacylglycerol accumulation in the post-ischemic canine heart after transient increase of plasma lipids. 914 Aug 7

The delayed phase ('second window') of protection induced by ischemic preconditioning in rabbit heart is observed as enhanced resilience to infarction 24 hours after repetitive brief cycles of ischemia. Here we provide a fuller physiological characterisation of this phenomenon in the open-chest rabbit model, examining temporal characteristics and dose-dependency of this adaptation. For examination of the timecourse of delayed protection, rabbits were pretreated with four 5 minute coronary artery occlusions (PC) or sham operation (SHAM). Twenty four, 48, 72 or 96 hours later, infarct size after 30 min coronary occlusion and 120 minutes reperfusion was assessed with TTC staining and expressed as a percentage of myocardial risk volume (I/R). I/R was reduced at 24 hours (SHAM 48.1 +/- 3.9% v PC 31.4 +/- 3.0%, P < 0.01), 48 hours (SHAM 41.9 +/- 3.0% v PC 19.6 +/- 6.3%, P < 0.01), and 72 hours (SHAM 39.8 +/- 3.4% v PC 17.2 +/- 2.5%, P < 0.01). No protection was observed 96 hours after preconditioning (SHAM 35.0 +/- 4.8% v PC 36.9 +/- 3.8%). In a further study, animals were pretreated with one, two or four 5 minute coronary occlusions (1 x 5 PC, 2 x 5 PC, 4 x 5 PC) and subjected to the infarction protocol 48 hours later. I/R was 44.5 +/- 4.3% in SHAM, 24.8 +/- 4.4% in 1 x 5 PC (P < 0.01), 27.4 +/- 2.9% in 2 x 5 PC (P < 0.05) and 24.4 +/- 4.8 in 4 x 5 PC (P < 0.01). Delayed protection in this rabbit model is prolonged, extending between 24 and 72 hours after the preconditioning stimulus. The threshold for eliciting the second window of protection in this model is as low as one 5 minute coronary occlusion.
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PMID:Characterisation of the infarct-limiting effect of delayed preconditioning: timecourse and dose-dependency studies in rabbit myocardium. 922 1

This study was designed to investigate whether a new irreversible injury to the myocardium can occur 6 hours after reperfusion following ischemia. Conscious rabbits were subjected to myocardial ischemia for 30 minutes, followed by reperfusion. Horseradish peroxidase (HPR) tracing with TTC staining and histological quantification were used to study the histopathological changes in myocardial tissues. Necrotic myocardium at 6 hours after reperfusion gave positive HRP results and viable myocardium at 24 hours after reperfusion gave positive TTC results. Some myocardial tissue between the above two regions were found to be HRP negative as well as TTC negative, indicating that myocardial tissue death occurred between 6 to 24 hours after reperfusion. The myocardial infarct size at 24, 48, and 72 hours after reperfusion were 7.0%, 5.1% and 3.2% larger than that 6, 24 and 48 hours respectively. Therefore, new irreversible myocardial injury in the rabbit can still occur after 6 hours of reperfusion following myocardial ischemia for 30 minutes and cumulative myocardial injury from 6 to 72 hours after reperfusion can result in a marked extension of the size of myocardial infarct.
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PMID:[A pathologic study of delayed myocardial reperfusion injury]. 927 61

Reduced brain tissue oxygenation is frequently seen in severe head injury and after subarachnoid hemorrhage, and this is considered a major cause of secondary ischemic brain injury. In fact, in a previous study, we found a tight correlation between low brain tissue oxygen tension and poor outcome. Therefore, we tested the hypothesis that an allosteric modifier of hemoglobin, which improves oxygen transport to tissue, could reduce the size of an acute infarct in a feline model of human stroke. This compound produces a shift in the hemoglobin dissociation curve to the right and therefore facilitates the unloading of oxygen during low oxygen tension. Seventeen adult cats were studied. Ischemic stroke was induced through a transorbital, permanent, middle cerebral artery occlusion. Seven animals received saline, and 10 received the allosteric Hb modifier RSR-13. Three different endpoints were used to determine the effect of the allosteric modifier. Delta p50 values were measured in the arterial blood; the intra-infarct oxygen tension was measured, and finally, the volume of the infarct was assessed using TTC staining. Mean delta p50 changes varied from 10.4 +/- 9.2 mmHg up to 15.0 +/- 6.8 mmHg. Mean intra-infarct oxygen tension was 27 +/- 6 mmHg for the control group and 33 +/- 7 mmHg for the drug-treated animals. The mean infarct size (measured as percentage of hemisphere volume) in the control group was 32 +/- 9% and for the RSR-13 animals 22 +/- 10% (p < 0.05). A definitive trend towards improvement in brain oxygen tension was seen, such that animals pretreated with RSR-13 showed a higher infarct oxygen tension. Infarct size was significantly reduced in the drug group. Therefore, RSR-13 is potentially beneficial in the treatment of brain ischemia. Since human studies with this compound are already completed, and other compounds which increase oxygen delivery, such as perfluorocarbons, are already being evaluated, it is likely that oxygen delivery enhancement will rapidly become the first 'neuroprotective' modality, employed in patients with severe brain injury, stroke and subarachnoid hemorrhage.
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PMID:The rationale for, and effects of oxygen delivery enhancement to ischemic brain in a feline model of human stroke. 936 91

TTC-909 (Clinprost), a chemically stable PGI2 analog, isocarbacyclin methyl ester (TEI-9090 or Clinprost) incorporated in lipid microspheres, when administered intravenously after brain ischemia, prevents ischemic neuronal damage possibly by modulating cerebral blood flow and platelet aggregation. However, the possibility exists that TEI-7165, which is the free acid form and a central metabolite of TEI-9090, has direct neurotrophic action in vivo, since TEI-7165 has been shown to block neuronal voltage-dependent Ca2+ channels in vitro, and a novel prostacyclin receptor showing high affinity with TEI-7165 has been detected in a variety of brain regions including the hippocampus. In the present study, we infused TEI-7165 for 7 days into the lateral ventricle of gerbils starting 2 h before or just after 3-min forebrain ischemia. TEI-7165 infusion prevented significantly the ischemia-induced shortening of response latency time as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the hippocampal CA1 region, as well as synapses within the strata moleculare, radiatum and oriens of the region, were significantly more numerous in gerbils infused with TEI-7165 than in those receiving vehicle infusion. TEI-7165 infusion did not affect hippocampal blood flow or temperature. These findings, together with the previously depicted accumulation of centrally administered [3H]TEI-7165 around hippocampal neurons, suggest that TEI-7165 has a direct neuroprotective action in brain ischemia.
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PMID:Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils. 937 1

Significance, origin and nature of posttraumatic brain edema are still being debated. Recently, a "controlled cortical impact injury" (CCII) was introduced to model traumatic brain injury. Purpose of this study was to investigate the development and nature of brain edema following CCII. Traumatic brain injury was applied to the intact dura of the left hemisphere in Sprague-Dawley rats (n = 52, 250-350 g b.w.). Ketamine/xylazine-anesthesia or inhalation-anesthesia were used. A pneumatic impactor with a diameter of 5 mm contused the temporo-parietal cortex with a velocity of 7 m/s and an impact depth of 2 mm. 24 hours post injury the brains were removed. Posttraumatic hemispheric swelling and water content were determined gravimetrically, Evans blue extravasation spectrophotometrically, area and volume of ischemia by staining with TTC. MRI studies were performed with T1-,T2- and diffusion-weighted sequences. Posttraumatic swelling following CCII was 14.3 +/- 3.1%. Brain water content increased to 82.5 +/- 0.5% in lesioned hemisphere compared to 79.9 +/- 0.2% in control hemisphere. Following TTC staining, the average ischemic tissue volume was 56.7 +/- 19.2 mm3. There was a moderate uptake of Evans blue into the lesioned hemisphere. MRI studies demonstrated edema in 35.4 +/- 9.5 mm3 of the lesioned hemisphere. Gd-DTPA was taken up early after trauma only. A significantly decreased ADC (apparent diffusion coefficient) indicates the cytotoxic (ischemic) component of edema in this model. In conclusion, CCII produces significant posttraumatic brain swelling and edema which is both, of vasogenic and cytotoxic nature. Thus, the CCII models the human cortical contusion more appropriately and opens new avenues for therapeutical studies focussing on cortical contusions.
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PMID:Characterisation of brain edema following "controlled cortical impact injury" in rats. 941 93

The effects of TTC-909, the isocarbacyclin methyl ester clinprost (CAS 88931-51-5), incorporated into lipid microspheres, on ischemia-induced decrease in norepinephrine (NE) contents in stroke-prone spontaneously hypertensive rats (SHR-SP) with an occluded middle cerebral artery (MCA) were examined. Occluding of MCA led to infarction limited to the cerebral cortex and also a severe decrease in NE contents in peripheral regions of the infarction. TTC-909 was injected immediately after MCA occlusion, and then daily for 6 consecutive days. As TTC-909 in a dose of 200 ng/kg significantly (p < 0.05) prevented decreases in NE contents, TTC-909 may have cytoprotective effects on neuronal damage related to ischemia in humans.
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PMID:Effects of the isocarbacyclin methyl ester clinprost incorporated into lipid microspheres, in focal ischemia of stroke-prone spontaneously hypertensive rats. 942 73

In rabbits, inhibition of either protein kinase C or protein tyrosine kinase abolishes the infarct size reduction achieved by ischemic preconditioning. In pigs, however, inhibition of protein kinase C does not attenuate ischemic preconditioning. The present study tested whether inhibition of protein tyrosine kinase alone or in combination with inhibition of protein kinase C interferes with ischemic preconditioning in pigs. In 29 enflurane-anesthetized pigs, the LAD was cannulated and perfused from an extracorporeal circuit. Protein tyrosine kinase and protein kinase C were inhibited by continuous intracoronary infusion of genistein (5x10(-6) mol/l) and staurosporine (10(-7) mol/l), respectively. Subendocardial blood flow (ENDO) was measured with microspheres. Infarct size was analysed by TTC staining (% of LV area at risk) following 90 min low-flow ischemia and 120 min reperfusion. In the presence of genistein, 90 min ischemia at an ENDO of 0.06+/-0.01 (+/-s.e.m.) ml/min/g resulted in an infarct size of 16.7+/-4.2% (n=8). With genistein, ischemic preconditioning by 10 min ischemia and 15 min reperfusion still reduced infarct size to 6.5+/-2.7% (ENDO: 0.05+/-0. 01 ml/min/g, n=7, P<0.05). In the presence of both genistein and staurosporine, infarct size following 90 min ischemia was 14.1+/-3. 6% (ENDO: 0.06+/-0.01 ml/min/g, n=7). With genistein and staurosporine, ischemic preconditioning no longer reduced infarct size significantly (11.5+/-3.1%, ENDO: 0.06+/-0.01 ml/min/g, n=7). The effective attenuation of ischemic preconditioning only by simultaneous inhibition of both, protein kinase C and protein tyrosine kinase, suggests a complex signal cascade involving both protein kinases.
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PMID:Prevention of ischemic preconditioning only by combined inhibition of protein kinase C and protein tyrosine kinase in pigs. 951 96


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