Dual isotope carotid scintigraphy in patients with amaurosis fugax attacks

Summary A new dual isotope scintigraphic (DISC) examination of the carotid arteries consisting of simultaneous injections of ¹¹¹In-labeled platelets and ^99mTc-labeled red cells was performed on eight male patients suffering from amaurosis fugax attacks. In concordance with the angiographically proven high percentage of significant extracranial carotid disease in patients with amaurosis fugax, six of the eight patients examined had an increased platelet accumulation in the carotid artery clinically affected. In one patient with normal angiography and one amaurosis fugax attack the platelet scintigraphy even revealed a pathological platelet accumulation in the ipsilateral carotid artery. These findings confirm the hypothesis that most amaurosis fugax attacks are due to arterio-arterial emboli originating from atherosclerotic plaques of the carotid bifurcation.     

Platelet deposition at carotid endarterectomy sites in humans

Following carotid endarterectomy, early postoperative thrombosis or late restenosis occurs in up to 20% of vessels. Both complications may be related to platelet mechanisms. To assess platelet deposition at endarterectomy sites, we injected indium-111 labelled platelets in 24 men less than 30 minutes after carotid endarterectomy, with subsequent imaging 24-96 hours later. To determine if deposition decreased over time, 12 patients had follow-up studies 0.5-24 months later. For comparison, 2 control groups were studied: 1) patients with noncarotid surgery (n = 6) and 2) normal young subjects without endarterectomy and without evidence of carotid disease (n = 12). Quantitative analysis was performed performed using a deposition index that compared activity in operated with unoperated sites in surgical patients or activity in the right with left carotid arteries in normal subjects. Patients with recent endarterectomy had a mean deposition index of 1.7 +/- 0.5 (range 1.2-3.5) compared with a similarly determined ratio of 1.1 +/- 0.1 in normal subjects and 1.2 +/- 0.1 in the surgical controls (both p less than or equal to 0.05 vs. acute endarterectomy). At follow-up after endarterectomy, the mean deposition index decreased to 1.0 +/- 0.1, documenting reduced platelet deposition over time. We conclude that the arterial injury of carotid endarterectomy results in early platelet deposition, which is no longer present in most patients who are studied late. These findings suggest a reduction in platelet thrombus formation with time and are compatible with reendothelialization of the endarterectomized surface. This model may be useful for the in vivo assessment of therapies designed to reduce platelet accumulation following endothelial injury in humans.     

Serum interleukin-6 is elevated in symptomatic carotid bifurcation disease

Introduction – The levels of circulating proinflammatory cytokines may express the extent of the inflammatory response and their participation in plaque progression and rupture needs to be evaluated. We aimed to investigate differences in circulating levels of proinflammatory cytokines and in plaque infiltration by macrophages between patients undergoing carotid endarterectomy for symptomatic and asymptomatic carotid atherosclerotic disease. Methods – One hundred nineteen patients (91 men and 28 women; mean age 66 ± 8 years; range 42–83 years) who underwent carotid endarterectomy for significant (>70%) carotid bifurcation stenosis were enrolled in this study. Patients were characterized as symptomatic (n = 62) or asymptomatic (n = 57) after neurological examination. Serum levels of interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), IL‐1β, serum amyloid A (SAA), and high‐sensitivity C‐reactive protein (hs‐CRP) were evaluated. Macrophage infiltration of the plaque was assessed quantitatively from endarterectomy specimens using the monoclonal antibody CD68. Results – Serum IL‐6 levels were significantly higher in patients with symptomatic compared with those with asymptomatic carotid disease (3.3 [2.0–6.5] pg/ml vs 2.5 [1.9–4.1] pg/ml, P = 0.02). TNF‐α, IL‐1β, SAA, and hs‐CRP levels did not differ significantly between the two groups. Symptomatic patients had also more intense macrophage accumulation in the carotid plaque compared with asymptomatic patients (0.6 ± 0.1% vs 0.4 ± 0.1%, P < 0.001). Although there were correlations between the levels of the different inflammatory markers, there were no correlation between any of them and the extent of plaque macrophage infiltration. Conclusion – Patients with symptomatic carotid atherosclerotic disease have elevated serum IL‐6 levels compared with asymptomatic patients. Symptomatic patients have also more intense macrophage infiltration of the atherosclerotic plaque suggesting that inflammatory process may contribute to the destabilization of the carotid plaque.     

The importance of carotid artery plaque disruption and hemorrhage

The event or mechanism that causes an asymptomatic atherosclerotic carotid artery to become symptomatic remains uncertain. Analysis of carotid endarterectomy surgical specimens from symptomatic patients has suggested that primary intraplaque hemorrhage is the most important initiating event. Reanalysis of several recent series of carotid endarterectomy specimens demonstrated that plaque disruption (ulceration) occurs as frequently as plaque hemorrhage, and that both processes are significantly more frequent in symptomatic as compared with asymptomatic endarterectomy specimens. A review of the coronary artery pathology literature reveals that plaque disruption is commonly present in patients with acute fatal myocardial infarction. It is widely asserted that coronary artery plaque disruption leads to luminal thrombosis and intraplaque hemorrhage. A similar sequence of events may occur in symptomatic carotid arteries.     

Effect of TRK-100, a stable orally active prostacyclin analogue, on platelet function and plaque size in atherothrombotic strokes

Patients with carotid atheromatous lesions were prospectively studied with indium-111 platelet imaging, platelet aggregability and B-mode real-time ultrasound tests to determine the short-term effects of orally active prostacyclin analogue TRK-100 (40 micrograms, three times daily for 4 weeks). To establish baseline values, all patients underwent indium-111 platelet imaging, platelet aggregation study and B-mode ultrasound. The results were positive for carotid plaque and platelet accumulation. Visual analysis showed repeated platelet scintigrams to be unchanged in five patients without antithrombotic therapy; repeated ultrasound studies showed no change in eight of ten plaques, while one showed progression and one regression of the plaque. In five TRK-100 treated patients, five of seven lesions with platelet accumulation at the baseline became negative, and two remained unchanged during the treatment; repeated B-mode ultrasound tests indicated eight of nine plaques remained unchanged, while one showed plaque size reduction. Quantitative analysis demonstrated that, TRK-100 significantly reduced the ADP aggregation (1 microM) from 55.2 +/- 21.3% to 24.0 +/- 14.7% (+/- SD; p less than 0.05) and the platelet accumulation index (25.7 +/- 17.2% vs 10.4 +/- 10.4%; p less than 0.05). However, there was no significant reduction in plaque scores during TRK-100 therapy compared with the baseline (2.70 +/- 2.75 mm vs 2.51 +/- 2.58 mm). The data obtained suggested that short-term TRK-100 therapy has an inhibitory effect on platelet accumulation in carotid atheroma but does not cause significant changes in plaque size.     

颈动脉超声在无症状脑梗死患者中的应用分析

目的分析无症状脑梗死患者的颈动脉超声特点及应用价值。方法选取2015-12—2016-11于我院接受治疗的无症状脑梗死患者40例(观察组),症状性脑梗死40例(症状组),另选取健康体检者32例为对照组,回顾性分析其颈动脉彩超特征。结果斑块检出率、IMT厚度、Crouse斑块积分及斑块形态3组组间比较差异均有统计学意义(P0.05);狭窄程度观察组与对照组比较差异有统计学意义(P0.05),观察组与症状组比较差异无统计学意义(P0.05);3组颈内动脉血流参数比较差异具有统计学意义(P0.05),颈总动脉血流参数观察组与症状组比较差异有统计学意义(P0.05),观察组与对照组比较差异无统计学意义(P0.05)。结论存在颈部动脉硬化及斑块但尚未明确诊断无症状脑梗死者,颈动脉彩超观察斑块的形态和性质尤为重要;诊断明确的无症状脑梗死患者,应常规筛查颈动脉超声评估斑块情况,定期监测颈动脉斑块及血流参数变化,给予早期干预,预防疾病进一步发展。     

Interrelation between plaque surface morphology and degree of stenosis on carotid angiograms and the risk of ischemic stroke in patients with symptomatic carotid stenosis. On behalf of the European Carotid Surgery Trialists' Collaborative Group

BACKGROUND AND PURPOSE: The risk of ischemic stroke distal to an atherothrombotic carotid stenosis increases with the degree of stenosis. The main mechanism of stroke is thought to be embolism from fissured or ruptured plaque, but there are few published data on the relationship between plaque morphology and severity of stenosis and their independent effects on the risk of ischemic stroke. We sought to determine the interrelation between plaque surface morphology, degree of carotid stenosis, and the risk of ipsilateral ischemic stroke. METHODS: Severity of stenosis and plaque surface morphology were assessed on angiograms of the symptomatic carotid artery in 3007 patients in the European Carotid Surgery Trial and were related to baseline clinical characteristics, pathological characteristics of plaques examined at endarterectomy, and the risks of carotid territory ipsilateral ischemic stroke and other vascular events on follow-up. RESULTS: The early risk of ipsilateral ischemic stroke on medical treatment was closely related to the degree of carotid stenosis. However, the initial degree of carotid stenosis was not predictive of strokes occurring >2 years after randomization. Angiographic plaque surface irregularity and plaque surface thrombus at endarterectomy increased in frequency as the degree of stenosis increased (both P<0.0001). However, the degree of stenosis was still predictive of the 2-year risk of stroke on medical treatment after correction for plaque surface irregularity. Angiographic plaque surface irregularity was an independent predictor of ipsilateral ischemic stroke on medical treatment at all degrees of stenosis (hazard ratio=1.80; 95% CI, 1. 14 to 2.83; P=0.01). This relationship was maintained when the analysis was confined to strokes occurring >2 years after randomization (hazard ratio=2.75; 95% CI, 1.30 to 5.80; P=0.01). Neither the degree of stenosis nor plaque surface irregularity was predictive of the "background" stroke risk after endarterectomy or the risk of nonstroke vascular events. CONCLUSIONS: Angiographic plaque surface irregularity is associated with an increased risk of ipsilateral ischemic stroke on medical treatment at all degrees of stenosis. The increase in stroke risk with degree of stenosis is partly accounted for by the parallel increase in plaque surface irregularity and thrombus formation, but the degree of narrowing of the vessel lumen is still an independent predictor of ischemic stroke within 2 years of presentation.     

Carotid plaque inflammation detected by 18F-fluorodeoxyglucose-positron emission tomography. Pilot study

OBJECTIVES: Inflammation is important in both the pathogenesis and outcome of atherosclerosis. Current imaging techniques provide anatomic data but no indication of plaque inflammation. We tested the hypothesis that plaque inflammation could be assessed in vivo by (18)FDG-PET and that plaque inflammation could increase the risk of recurrent vascular events and poor response to treatment in a pilot study. PATIENTS AND METHODS: Thirteen patients (median age 66.1 years [55-82 years]) with recent carotid territory TIA or ischemic stroke and internal carotid artery (ICA) stenosis > or =50% were studied. Angiography and (18)F-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) imaging were carried out in all patients. Treatment for carotid stenosis in each patient was selected by the attending physician and consisted in medical treatment, endarterectomy or stent placement. During 6 months of follow-up, the specific end points assessed were the occurrence of any stroke, death, or re-stenosis. RESULTS: Patients with symptomatic carotid atherosclerosis were imaged using (18)FDG-PET. Strong (18)FDG uptake (SUV> or =2.7) was seen in 11 of 13 (85%) carotid lesions. Among these patients two died during follow-up, 3 had recurrent non-fatal ipsilateral ischemic stroke and 1 patient who had undergone stenting had non-symptomatic re-stenosis in control studies. There was a significant correlation between the (18)FDG uptake and degree of ICA stenosis detected by angiography. CONCLUSION: Carotid atherosclerotic plaques contain a variable degree of inflammation which can be assessed in vivo by means of FDG and PET. The prognostic value of this marker is, however, still unclear and needs further study.     

Doppler microembolic signals predict ischemic recurrences in symptomatic carotid stenosis

OBJECTIVE: To assess if Doppler microembolic signals (MES) associated with > or = 60% symptomatic extracranial carotid stenosis may predict ischemic recurrences before endarterectomy or angioplasty. METHODS: All patients with > or = 60% carotid stenosis with symptoms in the preceding 2 months were prospectively considered. MES were identified using current criteria. All patients were followed-up until endarterectomy or angioplasty. RESULTS: We studied 50 patients, at a median of 7 days from their last symptom. Twenty patients showed MES (40.0%); median embolus rate was 4/h. During a median follow-up of 19 days 7 patients had recurrences (transient monocular blindness = 2; TIAs=4; stroke=1); 6 of them had shown MES. The association between recurrences and MES was significant (P=0.012). CONCLUSIONS: MES may identify patients with symptomatic carotid stenosis who are likely to suffer an ischemic recurrence before endarterectomy. This information may affect medical treatment and referral to the vascular surgeon.     

The Role of Neurosonology in the Diagnosis and Management of Patients with Carotid Artery Disease: A Review

Carotid artery disease (CAD) is a common cause of ischemic stroke with high rates of recurrence. Carotid endarterectomy (CEA) or carotid artery stenting (CAS) are highly recommended for the secondary prevention of symptomatic CAD during the first 14 days following the index event of transient ischemic attack or minor stroke. CEA or CAS may also be offered in selected cases with severe asymptomatic stenosis. Herein, we review the utility of neurosonology in the diagnosis and pre‐/peri‐interventional assessment of CAD patients who undergo carotid revascularization procedures. Carotid ultrasound may provide invaluable information on plaque echogenicity, ulceration, risk of thrombosis, and rupture. Transcranial Doppler or transcranial color‐coded sonography may further assist by mapping collateral circulation, evaluating the impairment of vasomotor reactivity, detecting microembolization, or reperfusion hemorrhage in real time. Neurosonology examinations are indispensable bedside tools assisting in the diagnosis, risk stratification, peri‐interventional monitoring, and follow‐up of patients with CAD.     

Stroke prediction and prevention by carotid endarterectomy: keep an eye on the doughnut and not just the hole.

Carotid endarterectomy is currently indicated for patients with severe symptomatic carotid stenosis because it halves the risk of stroke. However, it is expensive and potentially risky, and is performed unnecessarily in most of these patients. In order to improve the cost effectiveness of carotid endarterectomy, other predictors of stroke, in addition to the presence of recent focal neurological symptoms and the degree of carotid stenosis, need to be identified. Further research into the nature of the carotid atherosclerotic plaque and the clustering of systemic factors (infectious, inflammatory and vascular risk factors) that trigger inflammatory and morphological changes in the asymptomatic plaque and predispose it to rupture (with subsequent symptomatic thromboembolism) may yield powerful predictors of stroke which, when combined with the degree of stenosis and presence of focal neurological symptoms, may improve patient selection for carotid endarterectomy and its cost effectiveness.     

Effect of aspirin and ticlopidine on platelet deposition in carotid atherosclerosis: assessment by indium-111 platelet scintigraphy

The antiplatelet effects of aspirin and ticlopidine were studied by a dual-tracer method, using indium-111 labeled platelets and technetium-99m human serum albumin, in a group of 12 patients with suspected ischemic cerebrovascular disease. The magnitude of platelet accumulation at the carotid bifurcation was expressed as the ratio of radioactivity of indium-111 platelets deposited on the vascular wall to those circulating in the blood-pool (PAI, platelet accumulation index), 48 hr after injection of labeled platelets. PAI values were measured before (baseline studies) and after the antithrombotic therapies (aspirin studies: 325 mg bid for 22.3 +/- 1.3 days, ticlopidine studies: 100 mg tid for 21.8 +/- 2.1 days). At the baseline, the mean PAI value at 24 carotid bifurcations in the patient group was 15.7 +/- 15.3% (mean +/- S.D.) compared to -4.3 +/- 9.1 at 24 carotid bifurcations in 12 normal subjects (p less than 0.01). We defined the upper limit for a normal PAI (%) value to be +13.9, namely the mean PAI plus 2 SD for the carotid bifurcation in normal subjects and used this value for semiquantitative analysis. At the baseline, significant elevation of PAI (more than 13.9%; positive scintigram) was observed at 12 of 24 vessels, while 12 other regions were negative (less than 13.9%). In the lesions with positive scintigraphic results at the baseline, the mean PAI (%) value from the baseline, aspirin and ticlopidine studies was 29.5 +/- 7.0, 11.2 +/- 8.5 (p less than 0.01 versus baseline) and 21.4 +/- 21.3 (not significant from baseline), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

MMP-9 and/or TIMP as predictors of ischaemic stroke in patients with symptomatic and asymptomatic atherosclerotic stenosis of carotid artery treated by stenting or endarterectomy – A review

We still lack an optimal tool to predict ischaemic stroke in patients with symptomatic and asymptomatic carotid stenosis (CS). It has already been shown that patients at increased risk of ischaemic stroke can be identified based on the elevated plasma levels of metalloproteinases (MMPs) and reduced activity tissue inhibitor of metalloproteinase (TIMP). There are few studies presenting the role of MMP-9 and TIMP in ischaemic stroke both in patients with symptomatic and asymptomatic CS treated with stenting or endarterectomy, however we have not found any published review summarizing the role of abovementioned markers. MEDLINE was accessed via Pub Med, and searched for published studies that analyzed MMP-9 and TIMP levels in patients with asymptomatic and symptomatic internal carotid stenosis and/or examined these parameters as potential risk markers for ischaemic stroke. A total of 13 articles documenting the outcomes of patients with symptomatic or asymptomatic carotid stenosis treated by carotid stenting or endarterectomy, were analyzed. Statistically significant differences in the levels of MMP-9 and/or TIMP in patients with symptomatic and asymptomatic CS have been reported. Also the concentrations of MMP-9 and TIMP in CS patients subjected to stenting or endarterectomy were higher than in baseline group. Moreover higher levels of MMP-9 and decreased TIMP was reported to be associated with the risk of restenosis. This systematic review shows that available evidence regarding the dynamics of MMP-9 and TIMP levels may be a predictor of cerebrovascular events in both symptomatic and asymptomatic carotid stenosis in patients treated with stenting or endarterectomy.     

Plaque surface and microembolic signals in moderate carotid stenosis

We performed Transcranial Doppler Monitoring to detect microembolic signals (MES) in 47 patients with moderate (30%-69%) carotid stenosis proven by selective angiography. We compared the occurrence of MES with the clinical characteristics of stenosis (symptomatic or asymptomatic) and the angiographic plaque features (nonulcerated, deep ulceration, superficial ulceration, ulceration with flap, or ulceration without flap). For these cases there was no indication for endarterectomy, nevertheless we thought it would be useful to identify risk subgroups that might benefit from surgical treatment. MES were detected in 17.9% of the stenoses with a prevalence (p <. 01) in symptomatic cases (25%) compared to asymptomatic cases (14. 3%). There was a significant correlation of MES with plaque ulceration (p <.01) and particularly with ulceration without flap (p <.01). No difference between deep and superficial ulceration was observed. The availability of prospective data on this topic might be useful to select subgroups of patients with moderate carotid stenosis at risk for embolism.     

Four-dimensional ultrasonographic characterization of plaque surface motion in patients with symptomatic and asymptomatic carotid artery stenosis.

BACKGROUND AND PURPOSE: In vitro studies of atherosclerotic plaque fracture mechanics suggest that analysis of local variations in surface deformability may provide information on relative vulnerability to plaque fissuring or rupture. We investigated plaque surface deformations in patients with symptomatic and asymptomatic carotid artery disease using 4-dimensional ultrasonography and techniques for measuring optical flow. METHODS: Four-dimensional ultrasound examinations of carotid artery plaques were performed in 23 asymptomatic and 22 symptomatic patients with 50% to 90% stenosis of the internal carotid artery. Plaque surface motion during 1 cardiac cycle was computed with a hierarchical model-based motion estimator. Results were compared with plaque echogenicity and surface structure. RESULTS: Of the 45 patients examined, plaque surface motion estimates were obtained for 18 asymptomatic and 13 symptomatic patients. There were no significant differences in echogenicity or surface structure of asymptomatic and symptomatic plaques (P>0.05). Results of motion estimation showed that asymptomatic plaques had surface motion vectors of equal orientation and magnitude to those of the internal carotid artery, whereas symptomatic plaques demonstrated evidence of inherent plaque movement. There was no significant difference in maximal plaque velocity between symptomatic and asymptomatic plaques (P<0.14). Maximal discrepant surface velocity (MDSV) in symptomatic plaques was 3.85+/-1.26 mm/s (mean+/-SD), which was significantly higher (P<0.001) than MDSV of asymptomatic plaques with 0.58+/-0.42 mm/s (mean+/-SD). CONCLUSIONS: ++MDSV of carotid artery plaques is significantly different in asymptomatic and symptomatic disease. Further studies are warranted to determine whether plaque surface motion patterns can identify vulnerable plaques in patients with carotid artery stenosis.     

Serial measurement of surface expressions of CD63, P-selectin and CD40 ligand on platelets in atherosclerotic ischemic stroke. A possible role of CD40 ligand on platelets in atherosclerotic ischemic stroke

BACKGROUND: Platelet activation is a key step in the progression of atherosclerosis. The CD40 ligand (CD40L) on platelets may be a critical factor to develop the acute vascular events from atheroma. METHODS: To determine the role of CD40L on platelets in atherosclerotic ischemic stroke, we serially measured the expressions of CD63, P-selectin and CD40L on platelets in patients with atherosclerotic ischemic stroke (n = 25) and compared them with those in patients with asymptomatic carotid stenosis (n = 20) and in normal subjects (n = 24). RESULTS: The expressions of CD63 and P-selectin on platelets were significantly higher in patients with atherosclerotic ischemic stroke (n = 25) than in normal subjects (n = 24). The extents of surface expressions of CD63 and P-selectin on platelets showed no significant differences between atherosclerotic ischemic stroke and asymptomatic carotid stenosis. However, the CD40L expression on platelets was significantly higher in atherosclerotic ischemic stroke when compared to that in asymptomatic carotid stenosis. CONCLUSIONS: In our data, among the population with large artery atherosclerosis, the patients with symptomatic ischemic events showed a significantly elevated expression of CD40L on platelets compared to those without ischemic events. Therefore, the upregulation of CD40L on platelets may be a specific marker of platelet activation to provoke ischemic stroke from large artery atherosclerosis.     

Hypertensive patients with carotid artery plaque exhibit increased platelet aggregability

BACKGROUND: Platelets play an important role in myocardial infarction and ischemic stroke events, but whether platelet aggregability is related to early stage arteriosclerosis remains unclear. METHODS: We used a novel platelet counting system which makes it possible to detect spontaneous platelet aggregation, to evaluate the relationship between platelet aggregability and carotid artery arteriosclerosis in 125 outpatients with primary hypertension (46-73 years old: 65 men, 60 women). All subjects underwent carotid artery ultrasonography to determine whether plaque was present and to estimate intima-media thickness. RESULTS: Patients with carotid artery plaques (Plaque(+), n=63) were older and had higher systolic blood pressures than patients without plaques (Plaque(-), n=62), but no significant differences in sex, body mass index, diastolic blood pressure, plasma concentrations of glucose, total cholesterol, triglyceride, lipoprotein cholesterol, fibrinogen or the platelet count in whole blood were observed between Plaque(+) and Plaque(-) groups. Plaque(+) subjects showed greater spontaneous platelet aggregability and platelet aggregation induced by 2 microM or 0.5 microM of ADP or 0.3 microM of epinephrine than the Plaque(-) group. When age and systolic blood pressure were matched (n=52 in both groups), the Plaque(+) subjects exhibited greater platelet aggregability than the Plaque(-) subjects. Platelet aggregation induced by 2 microM of ADP showed statistical significant positive correlation coefficients with age, HbA1c and diastolic blood pressure. CONCLUSION: Our results indicate that hypertensive patients with carotid artery plaque have increased platelet aggregability. A prospective study is recommended to clarify whether this increase in platelet aggregability promotes the progression of arteriosclerosis.     

Accumulation of radiolabelled platelets and fibrin on the carotid artery of rabbits after angioplasty: effects of heparin and dipyridamole

We investigated the dynamic accumulation of platelets and fibrin after balloon injury of the carotid arteries in rabbits in vivo. In addition, effects of heparin and dipyridamole treatment were also tested. Autologous (99m)Tc-labelled platelet and (123)I-labelled fibrin accumulation was measured at one minute intervals for 4 hours following balloon injury of the carotid artery. Platelet accumulation occurred rapidly, with an approximately 125% increase occurring within 30 min after injury. There was no further activity for up to 4 hours. This accumulation could be inhibited with an intravenous infusion of PGI2 (500 ng/kg/hr). Fibrin accumulation occurred slowly and continuously over the 4 hour measurement period. Injection of an anti-fibrin antibody inhibited fibrin accumulation. Heparin (25 U/kg/hr for 4 hrs) administration resulted in a significant 82 +/- 19% and 68 +/- 13% reduction in platelet and fibrin accumulation, respectively. This dose of heparin was associated with a 2-fold prolongation of the aPTT. Dipyridamole (0.45 mg/kg/hr for 4 hrs) resulted in a 46 +/- 12% and 70 +/- 25% reduction of platelet and fibrin accumulation, respectively. Thus, we demonstrated that the dynamics of platelet and fibrin accumulation following balloon injury in rabbits are very different. The vessel wall continues to be thrombogenic for fibrin up to 4 hours after injury even though platelet accumulation has ceased after one hour. We conclude that the local thrombotic events following balloon injury are complex and that not only platelets but also fibrin is important in regulating responses to injury.     

Asymptomatic embolization predicts stroke and TIA risk in patients with carotid artery stenosis.

BACKGROUND AND PURPOSE: Improved methods of identifying patients at high risk of thromboembolism would allow improved targeting of therapy. One such situation is carotid artery stenosis. This is associated with an increased risk of stroke, which can be reduced by carotid endarterectomy. However, the risk-benefit ratio is low in patients with tight asymptomatic stenosis and moderate symptomatic stenosis. Most stroke in patients with carotid stenosis is believed to be embolic. Therefore, the detection of asymptomatic cerebral emboli using Doppler ultrasound may allow identification of a high-risk group. METHODS: Transcranial Doppler ultrasound was used to record for 1 hour the ipsilateral middle cerebral artery in 111 patients with >60% carotid artery stenosis (69 symptomatic, 42 asymptomatic). The Doppler audio signal was recorded onto digital audio tape for later analysis for embolic signals (ES) by an individual blinded to clinical details. In 67 subjects the relationship between ES and angiographically determined plaque ulceration was investigated. All subjects were followed up prospectively, and the relationship between ES and risk of future ipsilateral carotid artery territory ischemic events (TIA and stroke) was determined. RESULTS: ES were detected in 41(36.9%) subjects. In symptomatic patients there was a significant inverse relationship between the number of ES per hour and time elapsed since last symptoms (Spearman's rho=-0.2558, P=0.034). ES were more common in subjects with plaque ulceration, with a relative risk of 4. 94 (95% CI, 1.23 to 19.84; P=0.025) after controlling for both symptomatic status and degree of stenosis. The presence of ES at entry was predictive of TIA and stroke risk during follow up in both symptomatic (P=0.02) and asymptomatic patients (P=0.007). Considering all 111 patients, the presence of asymptomatic embolization was predictive of a further ischemic event, with an adjusted OR of 8.10 (95% CI, 1.58 to 41.57; P=0.01) after controlling for other cardiovascular risk factors, degree of stenosis, symptomatic status, and aspirin or warfarin use. CONCLUSIONS: Asymptomatic embolization in patients with carotid artery stenosis correlates with known markers of increased stroke risk and is an independent predictor of future stroke risk in patients with both symptomatic and asymptomatic carotid stenosis. It may allow identification of a high-risk group of patients who will particularly benefit from carotid endarterectomy. A large multicenter study is now required to confirm these findings.     

Lack of association between carotid plaque hematoma and ischemic cerebral symptoms

To investigate the association between carotid plaque hematoma and symptoms of cerebral ischemia a retrospective review of 200 consecutive carotid endarterectomies at the Neurological Institute of New York was carried out. Data analyzed included cerebral ischemic symptoms, angiographic findings, preoperative use of antithrombotic agents, and microscopic pathology of endarterectomy specimens. No association was found between ischemic symptoms ipsilateral to the endarterectomy and presence, size, or age of plaque hematomas. Plaque hematomas were less common among patients who took antithrombotic agents preoperatively than among those who did not. The presence of plaque hematoma was associated with angiographic carotid cross-sectional area stenosis of greater than 75%. Patients with stenosis of less than 75% were more likely than those with stenosis of greater than 75% to have ischemic symptoms ipsilateral to the endarterectomy, suggesting that criteria for surgical treatment of carotid atherosclerosis differ for those who are symptomatic vs. those who are asymptomatic. These results demonstrate the limitation of using a surgical series to extend causal inferences about the relation between plaque hematoma and cerebral ischemic symptoms to the general population of people with carotid atherosclerosis.