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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of delayed thrombolysis with recombinant tissue plasminogen activator was tested in an embolic stroke model. The carotid territory was embolized in 103 rats with fibrin-rich clots formed and washed in polyethylene tubes. Hemispheric cerebral blood flow before and after embolization was measured by the intra arterial 133Xe injection method. At five delay times, 15-240 min after embolization, 69 animals were treated with tissue plasminogen activator, 20 mg/kg, and 34 animals with saline. Carotid angiography displayed the grade of occlusion of the cerebral arterial supply before and after treatment. Brains were fixed after 2 days, evaluated neuropathologically, and infarct volume measured. Cerebral blood flow was reduced by 56-71% after embolization. Reperfusion induced by thrombolytic therapy was demonstrated by comparing the posttreatment angiography of the pooled five treatment groups to control animals. Thrombolytic therapy significantly reduced the infarct volume and improved the prekill clinical score by up to 2 h of treatment delay, and treatment might have been beneficial even after 4 h delay. Prolonging the delay of treatment increased the infarct volume (p < 0.001, Jonck-heere-Terpstra test). Only a few hemorrhagic complications were observed. Thus, thrombolytic therapy in embolic stroke induced recanalization. The effect on clinical outcome and infarct volume was dependent on delay time.
J Cereb Blood Flow Metab 1994 May
PMID:Effect of delayed thrombolysis with rt-PA in a rat embolic stroke model. 816 89

The need for an agent to quantitatively measure regional cerebral blood flow in humans using single photon emission computed tomography has led to the development of a new 99mTc-labeled agent: bicisate (ethyl cysteinate dimer). We have utilized an acute stroke model in the baboon to examine the ability of this agent to quantitatively measure regional cerebral blood flow in ischemic tissue. One hour after occlusion of either the left anterior cerebral or the middle cerebral artery, 99mTc-bicisate was administered intravenously, followed 20 min later by the measurement of local cerebral blood flow using iodo-[14C]antipyrine. With use of double-label autoradiography, the distribution of 99mTc-bicisate was correlated with the local cerebral blood flow images. A cerebral blood flow parameter was calculated from the 99mTc-bicisate tissue distribution and the arterial blood tracer concentration using an indicator fractionation model. For cerebral blood flows above approximately 40-50 ml 100 g-1 min-1, 99mTc-bicisate underestimates cerebral blood flow by as much as 20%, while for blood flows below approximately 15 ml 100 g-1 min-1, blood flow is overestimated by the 99mTc-bicisate distribution by an average of 3-4 ml 100 g-1 min-1. This apparent hyperfixation at very low blood flows may be related to a higher extraction of this tracer by ischemic tissue.
J Cereb Blood Flow Metab 1994 Jan
PMID:Correlation between 99mTc-bicisate and regional CBF measured with iodo-[14C]antipyrine in a primate focal ischemia model. 826 69

A multicenter study was performed in seven European centers comparing 99mTc-bicisate with 133Xe as a means of evaluating bicisate as a tracer of CBF distribution in humans. The same type of single photon emission computed tomography (SPECT) instrument (Tomomatic) was used in all centers. A total of 115 cases were collected, and of these 105 were considered technically adequate, comprising 18 normal subjects, 18 senile dementia, eight epilepsy, one brain tumor, eight chronic head trauma, and 52 stroke cases. As expected, bicisate gave better spatial resolution than Xe. Agreement between the results of the two methods was noted in 98 cases, but not in the remaining 7, all belonging to the stroke group. These seven all suffered from a subacute stroke (11-23 days after onset), and the disagreement in all cases consisted of bicisate showing low count rate in the area of the infarct and Xe a normal or elevated flow (luxury perfusion) as sign of spontaneous thrombolysis with reperfusion; in fact, these seven cases comprised all the reperfusion cases in the series. The results validate bicisate as a tracer of CBF in normal humans and in chronic brain diseases. Only in a subgroup of subacute stroke cases does bicisate not follow CBF, as it fails to show reperfusion hyperemia. This suggests the usefulness of bicisate in stroke cases, particularly in the subacute phase, where other SPECT methods often present difficulties due to reflow masking the size and the severity of the lesion.
J Cereb Blood Flow Metab 1994 Jan
PMID:99mTc-bicisate reliably images CBF in chronic brain diseases but fails to show reflow hyperemia in subacute stroke: report of a multicenter trial of 105 cases comparing 133Xe and 99mTc-bicisate (ECD, neurolite) measured by SPECT on same day. 826 71

To evaluate the cerebral distribution of 99mTc-ethyl cysteinate dimer (99mTc-ECD) at blood flow levels beyond the normal range, we investigated postischemic reperfusion and acetazolamide (Diamox) activation test in stroke patients. The postischemic reperfusion was studied in 10 patients who showed a postischemic hyperperfusion area on other single photon emission computed tomography (SPECT) studies using N-isopropyl-rho-[123I]iodoamphetamine ([123I]IMP), 99mTc-hexamethyl propyleneamine oxime (99mTc-HMPAO), or 133Xe. 99mTc-ECD SPECT demonstrated a hyperactive area in one case, an isoactive area in four, and a hypoactive area in five. Correlations with CT findings revealed hyperactive areas without any abnormality, isoactive areas with perifocal rim, perifocal edema, or diffuse cerebral edema, and hypoactive areas with an infarct core. The Diamox activation test was studied in eight other patients with atherothrombotic stroke, and a limitation in vasodilative capacity was classified into three grades: Gr. 0 (none to minimal), Gr. I (mild), and Gr. II (moderate). [123I]IMP SPECT showed Gr. II and limitation in all eight cases. However, 99mTc-ECD showed Gr. II in three cases and Gr. I in five, and 99mTc-HMPAO revealed Gr. II in two cases, Gr. I in three, and Gr. 0 in three. We suggest that a lack of retention of 99mTc-ECD in a postischemic reperfusion area indicates the severity of the initial brain damage. Although the limitation in vasodilative capacity under Diamox-activated conditions was underestimated using 99mTc-labeled CBF tracers as compared with [123I]IMP, a retention of 99mTc-ECD in the unaffected area with an increased CBF under Diamox activation could be relatively superior to 99mTc-HMPAO.
J Cereb Blood Flow Metab 1994 Jan
PMID:Assessment of postischemic reperfusion and diamox activation test in stroke using 99mTc-ECD SPECT. 826 72

To characterize a recently introduced cerebral perfusion tracer, 99mTc-bicisate, single photon emission computed tomography (SPECT) images of 99mTc-bicisate were compared with CBF images obtained by positron emission tomography (PET) using the 15O steady-state method in 10 cases of cerebrovascular disease and dementia. 99mTc-Bicisate SPECT and PET CBF images showed a similar distribution pattern except for two cases with subacute stroke, in which 99mTc-bicisate showed less uptake than CBF in the infarcted area where oxygen metabolism was severely diminished. Comparison of 99mTc-bicisate uptake and CBF in the other eight cases showed less contrast between high- and low-flow regions in 99mTc-bicisate SPECT. Although the SPECT count ratio of cerebral structures to cerebellum showed a good correlation with CBF ratio, it gradually deviated from the linear relationship in the high-flow range. Assuming this nonlinear relationship is due to the limited extraction of the tracer, we estimated the permeability-surface area product (PS) value by a nonlinear least-squares curve-fitting procedure. The correction of the nonlinear relationship using the estimated PS value and a table lookup method resulted in an excellent linear relationship between corrected SPECT counts and CBF.
J Cereb Blood Flow Metab 1994 Jan
PMID:Brain perfusion SPECT with 99mTc-bicisate: comparison with PET measurement and linearization based on permeability-surface area product model. 826 73

Single photon emission computed tomography (SPECT) using 99mTc-bicisate and N-isopropyl-p-[123I]iodoamphetamine ([123I]IMP) was compared in 25 patients suffering cerebral ischemia during the subacute phase (7-14 days) of stroke. Patients were classified as cortical strokes (15) and subcortical strokes (10) according to clinical and CT data. Images were analyzed by five independent blinded observers. Then, using a cross-matching method between normal and abnormal brain areas, we evaluated the sensitivity and specificity for 99mTc-bicisate and [123I]IMP and inter- and intraobserver reproducibility. A semiquantitative analysis was performed to compare abnormal hypoactive areas versus the corresponding contralateral areas for 99mTc-bicisate and [123I]IMP in the two patient groups. There was no significant difference for sensitivity and specificity between 99mTc-bicisate and [123I]IMP. Matching was approximately 90% in the two groups. The kappa-concordance index was satisfactory and slightly better for 99mTc-bicisate (0.485) than for [123I]IMP (0.435). Level of hypoactivity in the abnormal areas was significantly higher for 99mTc-bicisate (p < 0.03, n = 25) than for [123I]IMP, especially for cortical strokes. This comparative study demonstrates that 99mTc-bicisate is a very useful tracer for the detection of focal cerebral ischemia by SPECT during the subacute phase of stroke.
J Cereb Blood Flow Metab 1994 Jan
PMID:Comparison of brain SPECT using 99mTc-bicisate (L,L-ECD) and [123I]IMP in cortical and subcortical strokes. 826 76

99mTc-bicisate (99mTc-ECD) is a new brain perfusion imaging agent formulated from a radiochemically stable kit (Neurolite). A multicenter trial was conducted to determine the sensitivity and specificity of single photon emission computed tomography (SPECT) imaging with 99mTc-bicisate in the localization of ischemic stroke; 170 subjects were enrolled, 128 patients with stroke and 42 controls. Imaging results from 148 subjects (107 stroke patients and 41 controls) were considered evaluable. In the evaluable subjects, SPECT brain imaging with 99mTc-bicisate (21.0 +/- 2.5 mCi) was interpreted without clinical information and was compared with a final assessment using all clinical, diagnostic, and laboratory procedures except the 99mTc-bicisate SPECT results. 99mTc-bicisate was safe and well-tolerated. SPECT imaging with 99mTc-bicisate demonstrated a specificity of 98% and a sensitivity of 86% for localization of strokes (kappa, 0.75; 95% confidence interval, 0.64-0.86). Results were unchanged over time and were similar for all stroke mechanisms except for lacunar disease (sensitivity, 58%). In a secondary analysis, a normal image or small, deep (e.g., subcortical) perfusion defect was highly predictive of a lacunar mechanism. Defects involving the cortical surface were strongly associated with nonlacunar mechanisms. SPECT imaging with 99mTc-bicisate is a sensitive marker in the localization of perfusion defects associated with ischemic stroke and may assist in the determination of the underlying mechanism of a stroke.
J Cereb Blood Flow Metab 1994 Jan
PMID:The role of single photon emission computed tomography brain imaging with 99mTc-bicisate in the localization and definition of mechanism of ischemic stroke. 826 77

Autoradiograms obtained after middle cerebral artery occlusion (MCAO) in spontaneously hypertensive rats show that the 99mTc complex of a 2-nitroimidazole-derivatized propylene amine oxime (BMS-181321) is selectively retained in acutely ischemic brain before disruption of the blood-brain barrier (BBB), but not in the ischemic infarct. BMS-181321 is therefore a marker of ischemic tissue at risk of infarction and its uptake, unlike that of x-ray and magnetic resonance contrast agents, does not require disruption of the BBB. In keeping with this conclusion, we have found that the single-pass cerebral extraction fraction of BMS-181321 is 0.67 at normal rat whole-brain blood flow. Sequential single-photon emission computed tomographic images obtained from cats after MCAO show that the initial distribution of BMS-181321 approximates regional CBF and that selective retention subsequently produces a positive image within the ischemic territory. BMS-181321 is the first Tc complex able to indicate not only ischemia, but also ischemic tissue at risk of infarction. Use of this novel Tc complex to monitor biochemical events during ischemia may contribute to the clinical management of acute stroke.
J Cereb Blood Flow Metab 1993 Sep
PMID:Imaging ischemic tissue at risk of infarction during stroke. 836 Feb 82

Ornithine decarboxylase (ODC), a key enzyme in polyamine biosynthesis, is induced in ischemic tissue and may mediate vasogenic edema and delayed neuronal death. We determined the effects of alpha-difluoromethylornithine (DFMO), a specific inhibitor of ODC, on infarct size and ODC activity in a rat model of transient focal ischemia. DFMO blocked the ischemia-induced increase in ODC and significantly reduced infarct volumes by 57-45%, depending upon the treatment regimen. These studies suggest that polyamine metabolism plays a role in the development of cerebral infarction after focal ischemia and that DFMO may be useful in limiting injury after a stroke.
J Cereb Blood Flow Metab 1993 Nov
PMID:DFMO reduces cortical infarct volume after middle cerebral artery occlusion in the rat. 840 13

Local cerebral hemodynamics and oxygen metabolism were measured by positron emission tomography (PET) with the oxygen-15 (15O) steady-state method in baboons, immediately before (T0), 1 (T1), and 3-4 (T2) h after permanent middle cerebral artery occlusion (MCAO). At T1, there was a marked fall in both cerebral blood flow (CBF) and the CBF/cerebral blood volume (CBV) ratio in the occluded territory; these changes were sustained at T2, indicating stable reduction in cerebral perfusion pressure and lack of spontaneous reperfusion within this time range. Compared with preocclusion conditions, the oxygen extraction fraction (OEF) in the occluded territory was elevated at both T1 and T2, indicative of a persistent oligemia/ischemia for up to 3 h after MCAO. At T2, however, this OEF increase had lessened, concomitantly with a decline in cerebral metabolic rate of oxygen (CMRO2). This impairment of oxidative metabolism occurred earlier in the deep, compared with the cortical, MCA territories; in the latter, the CMRO2 was essentially preserved at T1 and only moderately reduced at T2, possibly suggesting prolonged viability. Finally, no significant changes in CBF or CMRO2 were observed in the contralateral MCA territory in this time range after MCAO. Despite methodological limitations (mainly partial volume effects related to PET imaging, which may have resulted in an underestimation of true changes and an overlooking of heterogeneous changes) our study demonstrates the feasibility of the combined PET-MCAO paradigm in baboons; this experimental approach should be valuable in investigating the pathophysiology and therapy of acute stroke.
J Cereb Blood Flow Metab 1993 05
PMID:PET study of changes in local brain hemodynamics and oxygen metabolism after unilateral middle cerebral artery occlusion in baboons. 847


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