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)

The aim of this study was to investigate the role of apoptosis or necrosis in the development of delayed infarct, and the relationship between the level of XIAP gene, caspase-3 activation and ischemic cell death following transient focal cerebral ischemia. Adult male Sprague-Dawley rats underwent right middle cerebral artery occlusion (MCAo) for 50 min and reperfusion for 0.5, 4, 8, 24 h, 3, 7, 14 days. On TTC-stained coronal sections, delayed infarct was observed to develop in the whole MCA territory, especially in frontoparietal cortex after ischemia. Near total infarct was shown in striatum 24 h after MCAo, while delayed infarct was evident in the cortex. By day 3, the infarct had progressively expanded to the nearly whole area of the frontoparietal cortex. Flow cytometric analysis of Annexin-V (marks apoptosis) and PI (propidium iodide, marks necrosis) labeling cells showed that MCAo dominantly induced necrosis in ischemic core, striatum. Apoptosis contributed to delayed infarct and cell death in the border zone, dorsolateral cortex and hippocampus. The time-course of caspase-3 activation was consistent with the changes of apoptosis and infarct following MCAo. Further RT-PCR experiments indicated that there was a biphasic regulation of XIAP in time- and region-dependent manner after ischemia. In the infarct core (striatum), following a transient and slight increase during 0.5 h to 4 h post-MCAo, expression of XIAP mRNA markedly decreased. On the other hand, a longer and larger upregulation of XIAP was observed at early time points in border zone (0.5 to 8 h, in dorsolateral cortex; 0.5 to 24 h in hippocampus), then the level of XIAP reduced. A negative correlation was observed between apoptosis and regulation of XIAP gene in these regions. Our findings suggest a possible association between expression of XIAP gene, apoptosis and delayed infarct following ischemia.
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PMID:Development of cerebral infarction, apoptotic cell death and expression of X-chromosome-linked inhibitor of apoptosis protein following focal cerebral ischemia in rats. 1613 48

It has been suggested that the beneficial effects of reperfusing the myocardium might be in part reversed by the occurrence of reperfusion injury. Oxidative stress was suggested to be implicating in the pathogenesis of ischemia-reperfusion (I/R) injury. Many antioxidative plants were shown to be cardioprotective in experimental models of myocardial ischemia-reperfusion (I/R) injury. The present study was designed to investigate the effects of pretreatment with alcoholic extract of Tinospora cordifolia in an in vivo rat model. The model adopted was that of surgically-induced myocardial ischemia, performed by means of left anterior descending coronary artery occlusion (LAD) for 30 min followed by reperfusion for another 4 h. Infarct size was measured by using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically by the methods developed by Yagi and Ohkawa et al. respectively. A lead II electrocardiogram was monitored at various intervals throughout the experiment. A dose dependent reduction in infarct size and in lipid peroxide levels of serum and heart tissue were observed with the prior treatment of T. cordifolia with various doses for 7 d compared to control animals. Hence, the present study suggests the cardioprotective activity of T. cordifolia in limiting ischemia-reperfusion induced myocardial infarction.
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PMID:Cardioprotective activity of alcoholic extract of Tinospora cordifolia in ischemia-reperfusion induced myocardial infarction in rats. 1632 73

Magnetic resonance imaging (MRI) can simultaneously detect and quantify myocardial dysfunction and shrinkage in contrast-enhanced areas postinfarction. This ability permits the investigation of our hypothesis that transformation of infracted myocardium to scarred tissue imposes additional burdens on peri-infarcted and remote myocardium. Pigs (n = 8) were subjected to reperfused infarction. Gd-DOTA-enhanced inversion recovery gradient echo sequence (IR-GRE) imaging was performed 3 days and 8 weeks postinfarction. Global and regional left ventricular (LV) function was evaluated by cine MRI. Triphenyltetrazolium chloride (TTC) stain was used to delineate infarction while hematoxylin and eosin (H & E) and Masson's trichrome stains were used to characterize remodeled myocardium. Late contrast-enhanced MRIs showed a decrease in the extent of enhanced areas from 17 +/- 2% at 3 days to13 +/- 1% LV mass at 8 weeks. TTC infarction size was 12 +/- 1% LV mass. Cine MRIs showed expansion in dysfunctional area due to unfavorable remodeling, ischemia, or strain. Ejection fraction was reduced in association with increased end-diastolic and end-systolic volumes. Scarred myocardium contained collagen fibers and remodeled thick-walled vessels embedded in collagen. Sequential MRI showed greater LV dysfunction despite the shrinkage in extent of enhanced areas 2 months postinfarction. The integration of late enhancement and cine MRI incorporates anatomical and functional evaluation of remodeled hearts.
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PMID:Scarred myocardium imposes additional burden on remote viable myocardium despite a reduction in the extent of area with late contrast MR enhancement. 1636 20

Recent studies have focused on elucidating the contribution of individual complement proteins to post-ischemic cellular injury. As the timing of complement activation and deposition after cerebral ischemia is not well understood, our study investigates the temporal pattern of C1q accumulation after experimental murine stroke. Brains were harvested from mice subjected to transient focal cerebral ischemia at 3, 6, 12, and 24 hr post reperfusion. Western blotting and light microscopy were employed to determine the temporal course of C1q protein accumulation and correlate this sequence with infarct evolution observed with TTC staining. Confocal microscopy was utilized to further characterize the cellular localization and characteristics of C1q deposition. Western Blot analysis showed that C1q protein begins to accumulate in the ischemic hemisphere between 3 and 6 hr post-ischemia. Light microscopy confirmed these findings, showing concurrent C1q protein staining of neurons. Confocal microscopy demonstrated co-localization of C1q protein with neuronal cell bodies as well as necrotic cellular debris. These experiments demonstrate the accumulation of C1q protein on neurons during the period of greatest infarct evolution. This data provides information regarding the optimal time window during which a potentially neuroprotective anti-C1q strategy is most likely to achieve therapeutic success.
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PMID:Temporal pattern of C1q deposition after transient focal cerebral ischemia. 1644 84

Thrombolysis with tissue plasminogen activator (tPA) is the only pharmacotherapy available for cerebral ischemia. However, the use of tPA can increase the risk of hemorrhage due to blood-brain barrier (BBB) breakdown. Recent evidence suggests that increased activation of matrix metalloproteinases (MMPs) may be involved in this breakdown. This study examines the temporal profile of MMP-2 and -9 following tPA administration to ischemic rats. Male Sprague-Dawley rats were randomly assigned to one of four groups (Sham-tPA; Sham-Saline; Ischemia-tPA; Ischemia-Saline; group n = 6, total N = 120). Focal embolic ischemia was induced by middle cerebral artery occlusion through injection of an autologous clot. One hour post-surgery, tPA (10 mg/kg) or saline was delivered intravenously and animals were euthanized at 3, 6, 12, or 24 h after onset of ischemia. Infarct volume was measured by TTC staining; BBB components examined immunohistochemically; and MMP activation measured by gelatin zymography. Our results show that tPA significantly reduced infarct volumes (overall infarct volume-Sham-tPA: 5.80 +/- 4.55 [mean +/- SE]; Sham-Saline: 5.00 +/- 4.23; Ischemia-tPA: 186.1 +/- 73.45; Ischemia-Saline: 284.8 +/- 88.74; all P < 0.05). Treatment with tPA was also associated with the activation of MMP-9 at 6, 12, and 24 h following ischemia. No temporal changes were observed in MMP-2 activation, although tPA administration increased its activity compared to saline treatment. Analyses of immunohistochemistry showed that destruction of components of the BBB followed MMP-9 activation. Thus, increased MMP-9 activation may, in part, be responsible for the increases in hemorrhagic transformation reported with use of tPA. Our study is the first to demonstrate the temporal profile of MMP activation following thrombolysis with tPA in a model of thrombotic focal cerebral ischemia.
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PMID:Matrix metalloproteinase activation and blood-brain barrier breakdown following thrombolysis. 1662 94

2,3,5,4'-tetra-hydroxystilbene-2-O-glucoside (THSG), the water-soluble active components extracted from dried tuber root of Polygonum multiflorum (Polygonaceae), can promote the release of nitric oxide (NO) from vascular endothelial cells and has strong antioxidation. The postconditioning's protection of THSG on cardiac ischemia-reperfusion injury and the mechanism were investigated. After reperfusion for 3 h following occlusion of rat left anterior descending coronary artery (LAD) for 30 min, SalphaT recovery speed, arrhythmia and cardiac infarct size were observed. The ischemic size and infarct size was identified by using Evans blue and TTC staining methods respectively. The results showed that the infarct size in THSG 7. 5 mg/kg postconditioning group was significantly decreased from 43.6% +/- 9.1% in mode group to 16.5% +/- 6.5% (P < 0.01). SalphaT recovery was quicker and the incidence of arrhythmia (55.6% vs 100%, P < 0.05) was significantly lower than in control group. The infarct size in THSG+glybenclamide group was greater than in THSG group, but equivalent to that in control group (46.8% +/- 9.8% vs 43.6% +/- 9.1%, P > 0.05), SalphaT recovery speed slower and the incidence of arrhythmia also lower (33.3% vs 100%, P < 0.01), suggesting that glybenclamide could abolish the effects of THSG postconditioning reducing the cardiac infart size. It was concluded that THSG administration before reperfusion could effectively alleviate the cardiac reperfusion injury and possessed the postconditioning effects of reducing cardiac infarct size, which might be related with the K(ATP) channel opening.
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PMID:Postconditioning's protection of THSG on cardiac ischemia-reperfusion injury and mechanism. 1671 27

Data on myocardial tolerance of ischemia in the animals with experimental diabetes are controversial. In our study, myocardial sensitivity to ischemia and infarction-limiting effect of ischemic preconditioning have been investigated in the in vivo rat model of myocardial infarction in alloxan-induced insulin-dependent diabetes mellitus. It has been shown that in 6 weeks after alloxan injection in the diabetic rats infarction size as determined by TTC staining was significantly smaller than in healthy controls (39.8 +/- 8.8 and 62.3 +/- 6.6%, respectively, p < 0.01). Also, occurrence of ischemic tachyarrhythmias was more rare in diabetic rats than in controls. A single episode of ischemic preconditioning in diabetic rats showed a much lesser protection against infarction than in controls. Therefore, the data obtained support the existence of endogenous protective myocardial phenotype in diabetes, although the effectiveness of ischemic preconditioning in diabetes is reduced.
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PMID:[Resistance of the myocardium to ischemia and efficacy of myocardial preconditioning in experimental diabetes mellitus]. 1673 37

T2 relaxation can augment delayed-enhancement viability imaging because it is sensitive to tissue edema and microcirculatory oxygen state. We demonstrate the T2 'signatures' of sub-lethal ischemia and stunning in porcine myocardium perfused by the distal left anterior descending artery, by imaging during percutaneous balloon occlusion for 25 minutes and subsequent reperfusion (n = 9). Muscle displayed ischemic dysfunction and partial post-ischemic functional recovery (p < or = 0.0004), concommitant with an elevated post-ischemic T2 (deltaT2 = 27 +/- 18%, p = 0.005). TTC staining verified muscle viability. The T2 fluctuations may reflect hyperemia and tissue cellular edema in accord with the known pathophysiology of ischemic and post-ischemic yet viable muscle.
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PMID:T2 fluctuations in ischemic and post-ischemic viable porcine myocardium in vivo. 1675 33

We have previously found that uridine 5'-triphosphate (UTP) significantly reduced cardiomyocyte death induced by hypoxia via activating P2Y(2) receptors. To explore the effect of UTP following myocardial infarction (MI) in vivo we studied four groups: sham with or without LAD ligation, injected with UTP (0.44microg/kg i.v.) 30min before MI, and UTP injection (4.4microg/kg i.v.) 24h prior to MI. Left ventricular end diastolic area (LVEDA), end systolic area (LVESA) fractional shortening (FS), and changes in posterior wall (PW) thickness were performed by echocardiography before and 24h after MI. In addition, we measured different biochemical markers of damage and infarct size using Evans blue and TTC staining. The increase in LVEDA and LVESA of the treated animals was significantly smaller when compared to the MI rats (p<0.01). Concomitantly, FS was higher in groups pretreated with UTP 30min or 24h (56+/-14.3 and 36.7+/-8.2%, p<0.01, respectively). Ratio of infarct size to area at risk was smaller in the UTP pretreated hearts than MI rats (22.9+/-6.6, 23.1+/-9.1%, versus 45.4+/-7.6%, respectively, p<0.001). Troponin T and ATP measurements, demonstrated reduced myocardial damage. Using Rhod-2-AM loaded cardiomyocytes, we found that UTP reduced mitochondrial calcium levels following hypoxia. In conclusion, early or late UTP preconditioning is effective, demonstrating reduced infarct size and superior myocardial function. The resulting cardioprotection following UTP treatment post ischemia demonstrates a reduction in mitochondrial calcium overload, which can explain the beneficial effect of UTP.
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PMID:Uridine-5'-triphosphate (UTP) reduces infarct size and improves rat heart function after myocardial infarct. 1693 82

The imaging appearances of 99Tc(m)-HL91, a new hypoxic imaging agent, in ischemic myocardium were studied and the value of 99Tc(m)-HL91 in the evaluation of regional ischemic viable myocardium was explored. Acute myocardial ischemia models were made by coronary artery legations in 18 rats and randomly divided into 2 groups: 99Tc(m)-HL91 group and 99Tc(m)-MIBI group. Evan blue infusion during ischemia and TTC staining after operation were used to delineate the area of ischemic and viable myocardium. The isolated heart was sliced in the short axis and then autoradiography was performed. The electron microscopic examination was also done for the myocardial samples. 99Tc(m)-HL91 and 99Tc(m)-MIBI uptake activities (counts/g) were measured in the area of ischemic myocardium (T) and normal myocardium (NT) separately. The uptake ratios of 99Tc(m)-HL91 and that of 99Tc(m)-MIBI in ischemic myocardium were calculated as T/NT. It was found that the normal myocardium was blue and ischemic or infarct myocardium was negative with Evans blue in all experiment rats. Both the normal and ischemic myocardium was in red color with TTC staining. In the 99Tc(m)-HL91 group the ischemic myocardium showed much higher uptake over normal myocardium, that was demonstrated both in the autoradiography and quantitative analysis. The ischemic/normal activity ratios were 1.634 +/- 0.354. It was suggested that 99Tc(m)-HL91 might accumulate in ischemic and viable myocardium, which is helpful in the evaluation of hypoxic but viable myocardium and potentially used as a imaging agent to assess myocardial viability.
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PMID:Detection of ischemic myocardium with a new hypoxic tissue targeting tracer 99Tc(m)-HL91. 1696 Dec 69


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