Factors associated with recurrent stroke and recanalization in patients presenting with isolated symptomatic carotid occlusion.

BACKGROUND AND PURPOSE: Patients with symptomatic internal carotid artery (ICA) occlusion constitute a small proportion of stroke/transient ischaemic attack patients who are at increased risk of early stroke recurrence and poor outcome. The optimal medical treatment for patients with symptomatic ICA occlusion who are ineligible for thrombolysis or thrombectomy is unknown. METHODS: Consecutive patients presenting at a single center with newly diagnosed symptomatic ICA occlusion (not involving the circle of Willis) were retrospectively reviewed. Those treated with intravenous thrombolysis or intra-arterial thrombolysis/thrombectomy were excluded. Patients were divided into two groups based on whether they experienced recurrent in-hospital stroke. RESULTS: The selected study population (n = 33) represented a small (20.4%) proportion of all newly symptomatic carotid occlusions, who nevertheless had an elevated risk of recurrent stroke during admission (24.2%). Of the variables examined (age, gender, admission National Institutes of Health Stroke Scale score, vascular risk factors, atrial fibrillation, prior stroke/transient ischaemic attack and anticoagulation within 48 h of presentation), only anticoagulation was significantly associated with a lower risk of in-hospital recurrent stroke. Anticoagulated patients showed a decreased incidence of stroke recurrence within the first week (6.7% vs. 38.9%, P = 0.032) and fewer strokes or deaths at 1 month (13.3% vs. 47.1%, P = 0.040). Hemorrhagic transformation was not observed in any patient. On follow-up imaging, ICA recanalization was significantly more frequent in anticoagulated patients (46.2% vs. 9.1%, P = 0.047). CONCLUSION: Patients with newly diagnosed symptomatic ICA occlusion (not involving the circle of Willis) represent a small but high risk subgroup of patients with carotid occlusion. Early anticoagulation was associated with fewer recurrent strokes and increased ICA recanalization. Larger scale prospective studies may be justified.

Carotid Stenting without Embolic Protection Increases Major Adverse Events: Analysis of the National Surgical Quality Improvement Program.

BACKGROUND AND PURPOSE: Published data regarding embolic protection device efficacy is mixed, and its use during carotid artery stent placement remains variable. We, therefore, examined the frequency of embolic protection device use and its association with outcomes after carotid artery stent placement using a national quality improvement data base. MATERIALS AND METHODS: Patients undergoing carotid artery stent placement with or without embolic protection devices were identified in the American College of Surgeons National Surgical Quality Improvement Program data base. The primary outcome was the incidence of major adverse cardiovascular events (defined as death, stroke, or myocardial infarction/arrhythmia) within 30 days. Propensity scoring was used to create 2 matching cohorts of patients using demographic and baseline variables. RESULTS: Between 2011 and 2018, among 1200 adult patients undergoing carotid artery stent placement, 23.8% did not have embolic protection devices. There was no trend toward increased embolic protection device use with time. Patients without embolic protection device use received preoperative antiplatelets less frequently (90.6% versus 94.6%, P = .02), underwent more emergent carotid artery stent placement (7.2% versus 3.6%, P = .01), and had a higher incidence of major adverse cardiovascular events (OR = 1.81; 95% CI, 1.11-2.94) and stroke (OR = 3.31; 95% CI, 1.71-6.39). After compensating for baseline imbalances using propensity-matched cohorts (n = 261 for both), carotid artery stent placement without an embolic protection device remained associated with increased major adverse cardiovascular events (9.2% versus 4.2%; OR = 2.30; 95% CI, 1.10-4.80) and stroke (6.5% versus 1.5%; OR = 4.48; 95% CI, 1.49-13.49). CONCLUSIONS: Lack of embolic protection device use during carotid artery stent placement is associated with a 4-fold increase in the likelihood of perioperative stroke. Nevertheless, nearly one-quarter of patients in the American College of Surgeons National Surgical Quality Improvement Program underwent unprotected carotid artery stent placement. Efforts targeting improved embolic protection device use during carotid artery stent placement are warranted.

Refractory Stroke Thrombectomy: Prevalence, Etiology, and Adjunctive Treatment in a North American Cohort.

BACKGROUND AND PURPOSE: Acute stroke intervention refractory to mechanical thrombectomy may be due to underlying vessel wall pathology including intracranial atherosclerotic disease and intracranial arterial dissection or recalcitrant emboli. We studied the prevalence and etiology of refractory thrombectomy, the safety and efficacy of adjunctive interventions in a North American-based cohort. MATERIALS AND METHODS: We performed a multicenter, retrospective study of refractory thrombectomy, defined as unsuccessful recanalization, vessel reocclusion in <72 hours, or required adjunctive antiplatelet glycoprotein IIb/IIIa inhibitors, intracranial angioplasty and/or stenting to achieve and maintain reperfusion. Clinical and imaging criteria differentiated etiologies for refractory thrombectomy. Baseline demographics, cerebrovascular risk factors, technical/clinical outcomes, and procedural safety/complications were compared between refractory and standard thrombectomy groups. Multivariable logistic regression analysis was performed to determine independent predictors of refractory thrombectomy. RESULTS: Refractory thrombectomy was identified in 25/302 cases (8.3%), correlated with diabetes (44% versus 22%, P = .02) as an independent predictor with OR = 2.72 (95% CI, 1.05-7.09; P = .04) and inversely correlated with atrial fibrillation (16% versus 45.7%, P = .005). Refractory etiologies were secondary to recalcitrant emboli (20%), intracranial atherosclerotic disease (60%), and/or intracranial arterial dissection (44%). Four (16%) patients were diagnosed with early vessel reocclusion, and 21 patients underwent adjunctive salvage interventions with glycoprotein IIb/IIIa inhibitor infusion alone (32%) or intracranial angioplasty and/or stenting (52%). There were no significant differences in TICI 2b/3 reperfusion efficacy (85.7% versus 90.9%, P = .48), symptomatic intracranial hemorrhage rates (0% versus 9%, P = .24), favorable clinical outcomes (39.1% versus 48.3%, P = .51), or mortality (13% versus 28.3%, P = .14) versus standard thrombectomy. CONCLUSIONS: Refractory stroke thrombectomy is encountered in <10% of cases, independently associated with diabetes, and related to underlying vessel wall pathology (intracranial atherosclerotic disease and/or intracranial arterial dissection) or, less commonly, recalcitrant emboli. Emergent salvage interventions with glycoprotein IIb/IIIa inhibitors or intracranial angioplasty and/or stenting are safe and effective adjunctive treatments.

Flow Diversion of Posterior Circulation Aneurysms: Systematic Review of Disaggregated Individual Patient Data.

BACKGROUND: Experience with endoluminal flow diversion for the treatment of posterior circulation aneurysms is limited. PURPOSE: We sought to investigate factors associated with the safety and efficacy of this treatment by collecting disaggregated patient-level data from the literature. DATA SOURCES: PubMed, EMBASE, and Ovid were searched up through 2019 for articles reporting flow diversion of posterior circulation aneurysms. STUDY SELECTION: Eighty-four studies reported disaggregated data for 301 separate posterior circulation aneurysms. DATA ANALYSIS: Patient, aneurysm, and treatment factors were collected for each patient. Outcomes included the occurrence of major complications, angiographic occlusion, and functional outcomes based on the mRS. DATA SYNTHESIS: Significant differences in aneurysm and treatment characteristics were seen among different locations. Major complications occurred in 22%, angiographic occlusion was reported in 65% (11.3 months of mean follow-up), and good functional outcomes (mRS 0-2) were achieved in 67% (13.3 months of mean follow-up). Multivariate analysis identified age, number of flow diverters used, size, and prior treatment to be associated with outcome measures. Meta-analysis combining the current study with prior large nondisaggregated series of posterior circulation aneurysms treated with flow diversion found a pooled incidence of 20% (n = 712 patients) major complications and 75% (n = 581 patients) angiographic occlusions. LIMITATIONS: This study design is susceptible to publication bias. Use of antiplatelet therapy was not uniformly reported. CONCLUSIONS: Endoluminal flow diversion is an important tool in the treatment of posterior circulation aneurysms. Patient age, aneurysm size, prior treatment, and the number of flow diverters used are important factors associated with complications and outcomes.

Comparison of Carotid Endarterectomy and Stenting for Symptomatic Internal Carotid Artery Near-Occlusion.

BACKGROUND AND PURPOSE: Carotid near-occlusion is defined as severe stenosis of the internal carotid artery with partial or full collapse of the distal vessel wall. The major studies evaluating carotid revascularization excluded patients with carotid near-occlusion. Given the paucity of data in the literature, we attempted to evaluate the safety of carotid endarterectomy and carotid artery stenting in carotid near-occlusion. MATERIALS AND METHODS: A retrospective data base review was performed from January 2010 to December 2018 to identify patients who underwent carotid endarterectomy or carotid artery stenting for symptomatic ICA near-occlusion and had 1-month clinical and imaging follow-up with carotid sonography. The medical records and imaging studies of patients with ICA near-occlusion were selected for analysis. RESULTS: Forty-five patients met the criteria for ICA near-occlusion, of whom 39 were included in the study, given insufficient 1-month follow-up on 6 patients. Of the 39 patients, 25 underwent carotid endarterectomy and 14 underwent carotid artery stenting. All patients had technically successful immediate revascularization of the ICA. Most (33 of 39) had 1-year follow-up postoperatively. Patients with carotid artery stenting had 20% restenosis and 79% vessel maturation rates, while patients with carotid endarterectomy had 17.4% restenosis and 84% vessel maturation. There was no significant difference in periprocedural complication rates between the 2 procedures. CONCLUSIONS: Carotid artery stenting shows similar outcomes in restenosis and vessel maturation rates compared with carotid endarterectomy for ICA near-occlusion. There were no major differences between the 2 treatments in clinical outcomes or periprocedural complications. Carotid artery stenting is a revascularization option for carotid near-occlusion if the patient is considered at high risk for carotid endarterectomy.

GUide sheath Advancement and aspiRation in the Distal petrocavernous internal carotid artery (GUARD) Technique during Thrombectomy Improves Reperfusion and Clinical Outcomes.

BACKGROUND AND PURPOSE: Adjunctive techniques to stent retriever thrombectomy include balloon-guide catheters and/or distal access catheters for aspiration. We describe a novel technique using a flexible, 6 French 088 distal guide sheath advanced past the skull base to augment mechanical thrombectomy. We studied the relative safety and efficacy of this technique in the setting of a combined stent retriever-distal access catheter aspiration thrombectomy protocol. MATERIALS AND METHODS: We performed a retrospective case-control study of intracranial internal carotid artery or M1-M2 middle cerebral artery occlusions requiring mechanical thrombectomy. Patients were divided into 2 groups based on thrombectomy techniques: conventional stent retriever with distal access catheter aspiration without (standard) and with adjunctive GUide sheath Advancement and aspiRation in the Distal petrocavernous internal carotid artery (GUARD). Using propensity score matching, we compared procedural safety, reperfusion efficacy using the modified Thrombolysis in Cerebral Infarction scale and clinical outcomes with the modified Rankin Scale. RESULTS: In comparing the GUARD (45 patients) versus standard (45 matched case controls) groups, there were no significant differences in demographics, NIHSS presentations, IV rtPA use, median onset-to-groin puncture times, procedural complications, symptomatic intracranial hemorrhage, or mortality. The GUARD group demonstrated significantly higher successful mTICI ≥2b reperfusion rates (98% versus 80%, P = .015) and improved functional mRS ≤2 outcomes (67% versus 43%, P = .04), with independent effects of the GUARD technique confirmed in a multivariable logistic regression model. CONCLUSIONS: The GUARD technique during mechanical thrombectomy with combined stent retrieval-distal access catheter aspiration is safe and effective in improving reperfusion and clinical outcomes.

Diagnostic Accuracy of High-Resolution Black-Blood MRI in the Evaluation of Intracranial Large-Vessel Arterial Occlusions.

BACKGROUND AND PURPOSE: 3D high-resolution black-blood MRI or MR vessel wall imaging allows evaluation of the intracranial arterial wall and extraluminal pathology. We investigated the diagnostic accuracy and reliability of black-blood MRI for the intraluminal detection of large-vessel arterial occlusions. MATERIALS AND METHODS: We retrospectively identified patients with intracranial arterial occlusions, confirmed by CTA or DSA, who also underwent 3D black-blood MRI with nonenhanced and contrast-enhanced T1 sampling perfection with application-optimized contrasts by using different flip angle evolution (T1 SPACE) sequences. Black-blood MRI findings were evaluated by 2 independent and blinded neuroradiologists. Large-vessel intracranial arterial segments were graded on a 3-point scale (grades 0-2) for intraluminal baseline T1 hyperintensity and contrast enhancement. Vessel segments were considered positive for arterial occlusion if focal weak (grade 1) or strong (grade 2) T1-hyperintense signal and/or enhancement replaced the normal intraluminal black-blood signal. RESULTS: Thirty-one patients with 38 intracranial arterial occlusions were studied. The median time interval between black-blood MRI and CTA/DSA reference standard studies was 2 days (range, 0-20 days). Interobserver agreement was good for T1 hyperintensity (κ = 0.63) and excellent for contrast enhancement (κ = 0.89). High sensitivity (100%) and specificity (99.8%) for intracranial arterial occlusion diagnosis was observed with either intraluminal T1 hyperintensity or contrast-enhancement imaging criteria on black-blood MRI. Strong grade 2 intraluminal enhancement was maintained in >80% of occlusions irrespective of location or chronicity. Relatively increased strong grade 2 intraluminal T1 hyperintensity was noted in chronic/incidental versus acute/subacute occlusions (45.5% versus 12.5%, P = .04). CONCLUSIONS: Black-blood MRI with or without contrast has high diagnostic accuracy and reliability in evaluating intracranial large-vessel arterial occlusions with near-equivalency to DSA and CTA.

Transmitter release increases intracellular calcium in perisynaptic Schwann cells in situ.

Glial cells isolated from the nervous system are sensitive to neurotransmitters and may therefore be involved in synaptic transmission. The sensitivity of individual perisynaptic Schwann cells to activity of a single synapse was investigated, in situ, at the frog neuromuscular junction by monitoring changes in intracellular Ca2+ in the Schwann cells. Motor nerve stimulation induced an increase in intracellular Ca2+ in these Schwann cells; this increase was greatly reduced when transmitter release was blocked. Furthermore, local application of the cotransmitters acetylcholine and ATP evoked Ca2+ responses even in the absence of extracellular Ca2+. Successive trains of nerve stimuli or applications of transmitters resulted in progressively smaller Ca2+ responses. We conclude that transmitter released during synaptic activity can evoke release of intracellular Ca2+ in perisynaptic Schwann cells. This Ca2+ signal may play a role in the maintenance or modulation of a synapse. These data show that synaptic transmission involves three cellular components with both postsynaptic and glial components responding to transmitter secretion.

Adjunctive Efficacy of Intra-Arterial Conebeam CT Angiography Relative to DSA in the Diagnosis and Surgical Planning of Micro-Arteriovenous Malformations.

BACKGROUND AND PURPOSE: Micro-arteriovenous malformations are an underrecognized etiology of intracranial hemorrhage. Our study aimed to assess the adjunctive efficacy of intra-arterial conebeam CTA relative to DSA in the diagnosis and surgical planning of intracranial micro-AVMs. MATERIALS AND METHODS: We performed a retrospective study of all micro-AVMs (≤1-cm nidus) at our institution. Blinded neuroradiologists qualitatively graded DSA and intra-arterial conebeam CTA images for the detection of specific micro-AVM anatomic parameters (arterial feeder, micronidus, and venous drainer) and defined an overall diagnostic value. Statistical and absolute differences in the overall diagnostic values defined the relative intra-arterial conebeam CTA diagnostic values, respectively. Blinded neurosurgeons reported their treatment approach after DSA and graded the adjunctive value of intra-arterial conebeam CTA to improve or modify treatment. Intra-arterial conebeam CTA efficacy was defined as interobserver agreement in the relative intra-arterial conebeam CTA diagnostic and/or treatment-planning value scores. RESULTS: Ten patients with micro-AVMs presented with neurologic deficits and/or intracranial hemorrhages. Both neuroradiologists assigned a higher overall intra-arterial conebeam CTA diagnostic value (P < .05), secondary to improved evaluation of both arterial feeders and the micronidus, with good interobserver agreement (τ = 0.66, P = .018) in the relative intra-arterial conebeam CTA diagnostic value. Both neurosurgeons reported that integrating the intra-arterial conebeam CTA data into their treatment plan would allow more confident localization for surgical/radiation treatment (8/10; altering the treatment plan in 1 patient), with good interobserver agreement in the relative intra-arterial conebeam CTA treatment planning value (τ = 0.73, P = .025). CONCLUSIONS: Adjunctive intra-arterial conebeam CTA techniques are more effective in the diagnostic identification and anatomic delineation of micro-AVMs, relative to DSA alone, with the potential to improve microsurgical or radiosurgery treatment planning.

Emergent Endovascular Management of Long-Segment and Flow-Limiting Carotid Artery Dissections in Acute Ischemic Stroke Intervention with Multiple Tandem Stents.

BACKGROUND AND PURPOSE: Although most cervical dissections are managed medically, emergent endovascular treatment may become necessary in the presence of intracranial large-vessel occlusions, flow-limiting and long-segment dissections with impending occlusion, and/or hypoperfusion-related ischemia at risk of infarction. We investigated the role of emergent endovascular stenting of long-segment carotid dissections in the acute ischemic stroke setting. MATERIALS AND METHODS: We retrospectively studied long-segment carotid dissections requiring stent reconstruction with multiple tandem stents (≥3 stents) and presenting with acute (<12 hours) ischemic stroke symptoms (NIHSS score, ≥4). We analyzed patient demographics, vascular risk factors, clinical presentations, imaging/angiographic findings, technical procedures/complications, and clinical outcomes. RESULTS: Fifteen patients (mean age, 51.5 years) with acute ischemic stroke (mean NIHSS score, 15) underwent endovascular stent reconstruction for vessel and/or ischemic tissue salvage. All carotid dissections presented with >70% flow limiting stenosis and involved the distal cervical ICA with a minimum length of 3.5 cm. Carotid stent reconstruction was successful in all patients with no residual stenosis or flow limitation. Nine patients (60%) harbored intracranial occlusions, and 6 patients (40%) required intra-arterial thrombolysis/thrombectomy, achieving 100% TICI 2b-3 reperfusion. Two procedural complications were limited to thromboembolic infarcts from in-stent thrombus and asymptomatic hemorrhagic infarct transformation (7% morbidity, 0% mortality). Angiographic and ultrasound follow-up confirmed normal carotid caliber and stent patency, with 2 cases of <20% in-stent stenosis. Early clinical improvement resulted in a mean discharge NIHSS score of 6, and 9/15 (60%) patients achieved a 90-day mRS of ≤2. CONCLUSIONS: Emergent stent reconstruction of long-segment and flow-limiting carotid dissections in acute ischemic stroke intervention is safe and effective, with favorable clinical outcomes, allowing successful thrombectomy, vessel salvage, restoration of cerebral perfusion, and/or prevention of recurrent thromboembolic stroke.

Differential time-course of slow afterhyperpolarizations and associated Ca2+ transients in rat CA1 pyramidal neurons: further dissociation by Ca2+ buffer.

Hippocampal neurons exhibit a slow afterhyperpolarization following membrane depolarization; this is thought to reflect an underlying Ca2+-dependent K+ current. This current is potentiated by intermediate concentrations (0.1-1.0 mM) of exogenous Ca2+ buffer [Schwindt P. C. et al. (1992) Neuroscience 47, 571-578; Zhang L. et al. (1995) J. Neurophysiol. 74, 2225-2241]. The relationship between the slow afterhyperpolarization and associated Ca2+ transients was investigated in the presence and absence of added exogenous Ca2+ buffer. Slow afterhyperpolarizations and underlying K+ currents were measured using whole-cell patch-clamp recordings from hippocampal CA1 neurons in acute rat brain slices. Inclusion of fluorescent Ca2+ indicators in the patch pipette solution allowed simultaneous measurement of the evoked subcellular Ca2+ transients using a confocal microscope. The peak Ca2+ signal exhibited an incremental increase with each action potential. This increase eventually reached a plateau with increasing numbers of action potentials, suggesting dye saturation with peak Ca2+ concentrations. As the K(D) for Ca2+ of the indicator dyes used was between 200 and 300 nM, it is predicted that saturation will occur when the peak Ca2+ signal exceeds 1 microM. This occurred with fewer action potentials in dendritic vs somatic compartments. Neither compartment exhibited averaged Ca2+ transients matching the slow afterhyperpolarization time-course, dendritic Ca2+ transients being most divergent. Intracellular accumulation of exogenous Ca2+ buffer, either by inclusion in the patch pipette or by incubation of the brain slice with its membrane-permeable form, caused a prolongation of the slow afterhyperpolarization but not of the somatic Ca2+ transient. The initial rate of decline of the dendritic Ca2+ transient was diminished, but remained faster than that of the slow afterhyperpolarization. We conclude that neither dendritic nor somatic Ca2+ signals match the slow afterhyperpolarization time-course, with this dissociation being further magnified by addition of exogenous Ca2+ buffer. The implications of this result are discussed.

Association of CT perfusion parameters with hemorrhagic transformation in acute ischemic stroke.

BACKGROUND AND PURPOSE: Prediction of hemorrhagic transformation in acute ischemic stroke could help determine treatment and prognostication. With increasing numbers of patients with acute ischemic stroke undergoing multimodal CT imaging, we examined whether CT perfusion could predict hemorrhagic transformation in acute ischemic stroke. MATERIALS AND METHODS: Patients with acute ischemic stroke who underwent CTP scanning within 12 hours of symptom onset were examined. Patients with and without hemorrhagic transformation were defined as cases and controls, respectively, and were matched as to IV rtPA administration and presentation NIHSS score (± 2). Relative mean transit time, relative CBF, and relative CBV values were calculated from CTP maps and normalized to the contralateral side. Receiver operating characteristic analysis curves were created, and threshold values for significant CTP parameters were obtained to predict hemorrhagic transformation. RESULTS: Of 83 patients with acute ischemic stroke, 16 developed hemorrhagic transformation (19.28%). By matching, 38 controls were found for only 14 patients with hemorrhagic transformation. Among the matched patients with hemorrhagic transformation, 13 developed hemorrhagic infarction (6 hemorrhagic infarction 1 and 7 hemorrhagic infarction 2) and 1 developed parenchymal hematoma 2. There was no significant difference between cases and controls with respect to age, sex, time to presentation from symptom onset, and comorbidities. Cases had significantly lower median rCBV (8% lower) compared with controls (11% higher) (P = .009; odds ratio, 1.14 for a 0.1-U decrease in rCBV). There was no difference in median total volume of ischemia, rMTT, and rCBF among cases and controls. The area under the receiver operating characteristic was computed to be 0.83 (standard error, 0.08), with a cutoff point for rCBV of 1.09. CONCLUSIONS: Of the examined CTP parameters, only lower rCBV was found to be significantly associated with a relatively higher chance of hemorrhagic transformation.

Emergency noninvasive angiography for acute intracerebral hemorrhage.

Spontaneous ICH is a devastating condition and is associated with significant mortality in the acute phase due to ongoing hemorrhage and hematoma expansion. A growing body of evidence suggests that there may be considerable utility in performing noninvasive vascular imaging during the acute-to-early phase of ICH. CTA has become widely available and is sensitive and specific for detecting vascular causes of secondary ICH such as aneurysms, arteriovenous malformations, dural arteriovenous fistulas, intracranial dissections, and neoplasm. CT venography can also diagnose dural sinus thrombosis presenting as hemorrhagic infarction. Recent data from stroke populations demonstrate a relatively low risk to patients when contrast is administered in the absence of a known serum creatinine. Detection of acute contrast extravasation within the hematoma ("spot sign") with CT angiography is predictive of subsequent hematoma expansion and is associated with increased morbidity and mortality. Risk stratification based on acute CTA can inform and expedite decision-making regarding intensive care unit admission, blood pressure control, correction of coagulopathy, and neurosurgical consultation. Noninvasive vascular imaging should be considered as an important component of the initial diagnostic work-up for patients presenting with acute ICH.

Does current practice in the United States of carotid artery stent placement benefit asymptomatic octogenarians?

BACKGROUND AND PURPOSE: CAS or CEA for asymptomatic carotid stenosis is the focus of recently completed and ongoing randomized clinical trials. These techniques are widely utilized outside the setting of such trials. Therefore, our goal was to analyze the in-hospital stroke or death rates after CAS or CEA for asymptomatic stenosis that reflect current nationwide practice. MATERIALS AND METHODS: Using sample-weighted ANOVA, we analyzed records from the 2006 and 2007 NIS, which are nationally representative cohorts for asymptomatic CAS or CEA. The primary outcome measure was a composite end point of in-hospital stroke, cardiac complications, or death. In-hospital stroke or death was a secondary outcome measure. RESULTS: For ≥ 80 years of age, the in-hospital stroke, cardiac complications, or death rate after CAS was 4.9%, while the complication rate after CEA was 3.8%. The stroke or death rate after CAS was 2.7% for ≥ 80 years of age and was 1.5% after CEA for the same age group. Multivariate analysis showed that age (OR, 1.12; 95% CI, 0.97-1.3; P < .07) or procedure (OR, 1.12; 95% CI, 0.99-1.27; P < .14) was not associated with the composite end point of in-hospital stroke, cardiac complications, or death. In contrast, CAS (OR, 1.28; 95% CI, 1.03-1.58) and female sex (OR, 1.23; 95% CI, 1.04-1.45) were independently associated with in-hospital stroke or death following asymptomatic carotid revascularization. Hospital charges and hospital costs were lower for CEA than CAS (2007 costs: $7779 versus $12,104). CONCLUSIONS: CAS is independently associated with increased in-hospital stroke or death (excluding cardiac complications from the composite outcome). In those ≥ 80 years of age, CAS as currently performed may not improve the natural history of asymptomatic carotid stenosis, because in-hospital stroke or death rates following CAS approached 3% in this group.

Muscarinic Ca2+ responses resistant to muscarinic antagonists at perisynaptic Schwann cells of the frog neuromuscular junction.

1. Acetylcholine causes a rise of intracellular Ca2+ in perisynaptic Schwann cells (PSCs) of the frog neuromuscular junction. The signalling pathway was characterized using the fluorescent Ca2+ indicator fluo-3 and fluorescence microscopy. 2. Nicotinic antagonists had no effect on Ca2+ responses evoked by ACh and no Ca2+ responses were evoked with the nicotinic agonist nicotine. The muscarinic agonists muscarine and oxotremorine-M induced Ca2+ signals in PSCs. 3. Ca2+ responses remained unchanged when extracellular Ca2+ was removed, indicating that they are due to the release of Ca2+ from internal stores. Incubation with pertussis toxin did not alter the Ca2+ signals induced by muscarine, but did block depression of transmitter release induced by adenosine and prevented Ca2+ responses in PSCs induced by adenosine. 4. The general muscarinic antagonists atropine, quinuclidinyl benzilate and N-methyl-scopolamine failed to block Ca2+ responses to muscarinic agonists. Atropine (at 20,000-fold excess concentration) also failed to reduce the proportion of cells responding to a threshold muscarine concentration sufficient to cause responses in less than 50% of cells. Only the allosteric, non-specific blocker, gallamine (1-10 microM) was effective in blocking muscarine-induced Ca2+ responses. 5. In preparations denervated 7 days prior to experiments, low concentrations of atropine reversibly and completely blocked Ca2+ responses to muscarine. 6. The lack of blockade by general muscarinic antagonists in innervated, in situ preparations suggests that muscarinic Ca2+ responses at PSCs are not mediated by any of the five known muscarinic receptors or that post-translational modification prevented antagonist binding.

Angiographic, hemodynamic and histological characterization of an arteriovenous fistula in rats.

BACKGROUND: Our understanding of the pathogenesis of arteriovenous malformations (AVMs) and arteriovenous fistulas (AVFs) has been limited by the lack of adequate animal models. In this study we evaluate the time course of angiographic, hemodynamic and histopathological changes in an arteriovenous fistula in rats as a potential model. METHODS: An arteriovenous fistula was created by a side-to-end anastomosis of the common carotid artery (CCA) to the external jugular vein (EJV). The animals underwent angiography of the fistula and were sacrificed 1, 7, 21, 42 or 90 days later. Flow and pressure measurements were performed in the CCA and ipsi- and contralateral EJV and detailed histological examination of whole mount sections of the fistula and cranium were done on fixed sections. Immunohistochemistry for CD31, smooth muscle alpha-actin and Ki-67 were performed. FINDINGS: Hemodynamic changes occur immediately after fistula formation creating a stable high flow, low resistant state. This induces a gradual increase in the inner diameter of the EJV and transverse sinus followed by a decrease in size of the transverse sinus. This decrease is associated with increased expression of alpha-actin in the wall of the sinus. The fistula becomes angiographically and histologically stable after 21 days. CONCLUSION: This model describes the time course of hemodynamic and histopathological changes after occur after AVF formation. Stabilization after 21 days makes it an attractive model for mechanistic and therapeutic studies of AVFs.