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Andrew J Ringer

Publications and source records attributed to Andrew J Ringer.

12 recordsLinked to original sources

Intraarterial reteplase and intravenous abciximab for treatment of acute ischemic stroke. A preliminary feasibility and safety study in a non-human primate model.

We performed a preliminary feasibility and safety study using intravenous (IV) administration of a platelet glycoprotein IIb/IIIa inhibitor (abciximab) in conjunction with intraarterial (IA) administration of a thrombolytic agent (reteplase) in a primate model of intracranial thrombosis. We introduced thrombus through superselective catheterization of the intracranial segment of the internal carotid artery in 16 primates. The animals were randomly assigned to receive IA reteplase and IV abciximab ( n =4), IA reteplase and IV placebo ( n =4), IA placebo and IV abciximab ( n =4) or IA and IV placebo ( n =4). Recanalization was assessed by serial angiography during the 6-h period after initiation of treatment. Postmortem magnetic resonance (MR) imaging was performed to determine the presence of cerebral infarction or intracranial hemorrhage. Partial or complete recanalization at 6 h after initiation of treatment (decrease of two or more points in pre-treatment angiographic occlusion grade) was observed in two animals treated with IA reteplase and IV abciximab, three animals treated with IA reteplase alone and one animal treated with IV abciximab alone. No improvement in perfusion was observed in animals that received IV and IA placebo. Cerebral infarction was demonstrated on postmortem MR imaging in three animals that received IA and IV placebo and in one animal each from the groups that received IA reteplase and IV abciximab or IV abciximab alone. One animal that received IV abciximab alone had a small intracerebral hemorrhage on MR imaging. IA reteplase with or without abciximab appeared to be the most effective regimen for achieving recanalization in our model of intracranial thrombosis. Further studies are required in experimental models to determine the optimal dose, method of administration and efficacy of these medications in acute ischemic stroke.

Abciximab↗

Clinical and angiographic results of dilatation procedures for symptomatic intracranial atherosclerotic disease.

BACKGROUND AND PURPOSE: The authors determined the technical success and the clinical and angiographic results of angioplasty and/or stent placement for intracranial atherosclerotic disease (ICAD) at a tertiary-care referral hospital. METHODS: Angiographic and clinical outcomes occurring within the 1-month follow-up interval were recorded. Patients were followed up for a mean period of 20.5 +/- 9.2 months, and a neurovascular imaging study was performed in 18 of the 21 patients alive after a mean period of 19.7 +/- 9.2 months. Stroke-free survival and ipsilateral stroke-prevention rates were estimated using Kaplan Meier analyses. RESULTS: Twenty-four patients (mean age = 61.0 +/- 13.5 years; 15 were men) underwent 30 procedures for treatment of ICAD. The procedures included angioplasty (n = 18) and attempted primary stent placement (n = 14). In 2 procedures, angioplasty was performed in the same session after unsuccessful stent placement. There was immediate stenosis reduction (mean +/- SD) from 84% +/- 17% to 27% +/- 21%. The overall 1-month composite rate of major stroke, death, and major bleeding complications was 7% for the 30 procedures. Overall stroke-free survival at 36 months was estimated as 79% (95% confidence interval, 57%-91%), and the ipsilateral stroke-prevention rate was estimated to be 87% (95% confidence interval, 65%-95%). Among the 15 patients who underwent repeat angiography, restenosis requiring second intervention was observed in 1 patient. No restenosis could be identified in 3 patients who underwent computed tomographic or magnetic resonance angiography. CONCLUSION: This single-center study demonstrates the feasibility and effectiveness (for secondary stroke prevention) of angioplasty and/or stent placement for treatment of ICAD.

Angiography, Digital Subtraction↗

Site-specific thromboembolism: a novel animal model for stroke.

BACKGROUND AND PURPOSE: To develop a technique for site-specific placement of a thrombus of predetermined volume in an animal model for the purpose of evaluating methods of intravascular thrombolysis and clot retrieval. METHODS: Six swine were subjected to thrombus injection bilaterally in the ascending pharyngeal artery (APA). Each animal underwent transfemoral angiography while under general anesthesia. A nondetachable balloon catheter and a 3-French microcatheter were then advanced into the common carotid artery through a 7-French guide catheter. With the microcatheter in the proximal APA and the balloon inflated proximally, a bolus of preformed thrombus composed of 0.9 mL of autologous blood and 0.1 mL of bovine thrombin (200 IU/mL) was injected through the microcatheter while local flow arrest was maintained for 15 min. The balloon was deflated and removed. The occluded arteries were observed by serial angiography for 3 hr and then resected for gross examination and hematoxylin and eosin staining. RESULTS: Each APA was occluded angiographically and did not recanalize during the 3-hr observation period. Persistent, proximal progression of thrombus to the superior thyroid artery origin occurred in three animals. Gross inspection revealed that the resected arteries contained thrombus in the proximal APA but not in the common carotid artery. Histologic examination revealed organized thrombus, without evidence of intimal injury. CONCLUSION: Our model provides a simple, reliable method for site-specific injection of a thrombus of predetermined volume. Site-specific placement is important for evaluation of the efficacy of thrombolytic agents and techniques. Angiographic evidence of brain revascularization can be used to grade revascularization and clot volume. The ability to specifically localize and estimate clot volume makes our model well suited for the evaluation and comparison of thrombolytic agents and endovascular techniques.

Angiography, Digital Subtraction↗

Fate of branch arteries after intracranial stenting.

OBJECTIVE: One concern with respect to stent procedures performed to treat patients with intracranial lesions is the fate of normal major arterial branches after stents are placed across them. Because most of these lesions occur at vessel bifurcations or at branch points, a normal major branch often arises near the lesion and may be difficult to avoid during stent positioning. The aim of this article is to describe the angiographic outcome of intracranial major branch arteries crossed by a stent in the intracranial circulation. METHODS: We examined the immediate postprocedural cerebral angiograms of the 40 patients who underwent intracranial stenting at the University at Buffalo, Buffalo, NY, between June 1998 and April 2000. In each of 10 patients, the stent was placed across a normal major branch artery. Stents were used to treat aneurysms in seven patients and intracranial stenosis in three patients. The latest cerebral angiogram available was reviewed, and the patency of the major branch arteries was evaluated. RESULTS: The angiographic follow-up period ranged from 4 days to 35 months (mean follow-up, 10 mo). Each of the 10 major branch arteries was patent. No infarcts were associated with the territory of the major branch arteries crossed by the stents, and no patient experienced a related episode of clinical ischemia. Four patients died as a result of causes unrelated to the stenting procedure. The histology of a middle cerebral artery stent that was placed across a lenticulostriate perforator is presented. CONCLUSION: The flexible, low-profile stents used in this study had no angiographically or clinically apparent effect on the major intracranial branches across which they were placed.

Adult↗

Regional intraparenchymal pressure differences in experimental intracerebral hemorrhage: effect of hypertonic saline.

OBJECTIVE: To study regional intraparenchymal pressures within the cranial cavity during and after formation of intracerebral hemorrhage. We also assessed the effect of hypertonic saline on intraparenchymal pressure in different brain regions and on regional brain distribution of sodium within the brain. DESIGN: Prospective, controlled, laboratory trial. SETTINGS: Animal research laboratory. SUBJECTS: Eight mongrel dogs, weighing 15-25 kg. INTERVENTION: We introduced an intracerebral hematoma in eight mongrel dogs by infusing 6 mL of autologous arterial blood in the deep white matter adjacent to the basal ganglia. Sodium chloride (23.4%, 1.4 mL/kg) then was administered intravenously 6 hrs after introduction of hematoma. MEASUREMENTS AND MAIN RESULTS: Parenchymal pressure monitors were placed in the perihematoma region, both frontal lobes, and the cerebellum to record intraparenchymal pressure during and 6 hrs after intracerebral hematoma formation. Intraparenchymal pressure measurements were recorded for 3 more hours after administration of 23.4% sodium chloride. Regional cerebral perfusion pressure was calculated for each intraparenchymal pressure measurement. Regional sodium distribution was measured in extracts from brain regions by using ion selective electrode technique. A higher elevation in intraparenchymal pressure was recorded in the perihematoma region during the introduction of the hematoma compared with other compartments. After 5 mL of autologous blood was introduced, intraparenchymal pressure (mm Hg +/- SE) was significantly higher in the perihematoma region (42.1 +/- 3.5) than in the ipsilateral (30.0 +/- 4.6, p <.05) and contralateral (27.1 +/- 5.5, p <.01) frontal lobes and cerebellum (29.1 +/- 4.5, p <.05). Four hours after introduction of the hematoma, the cerebral perfusion pressure recorded in the perihematoma region (43.6 +/- 9.7) remained significantly lower than in the ipsilateral (58.6 +/- 9.3, p <.05) but not the contralateral frontal lobes (54.7 +/- 10.1) and cerebellum (51.0 +/- 11.1). Administration of 23.4% sodium chloride immediately reduced intraparenchymal pressure in each compartment. This effect was still observed at 3 hrs in each compartment. Sodium concentration was higher in the perihematoma region than in the frontal lobes, cerebellum, or brain stem. CONCLUSIONS: Prominent differences were observed in intraparenchymal pressure and cerebral perfusion pressure in the perihematoma region and frontal lobes during and after intracerebral hematoma. We speculate that the potential importance of regional intraparenchymal pressure differences in the clinical settings may be under appreciated. In this canine model of intracerebral hematoma, a single dose of hypertonic saline effectively reduces the intraparenchymal pressure in all regions of the brain.

Analysis of Variance↗

Carotid angioplasty and stent placement: a prospective analysis of perioperative complications and impact of intravenously administered abciximab.

OBJECTIVE: To determine the frequency of perioperative complications since the introduction of abciximab, we prospectively evaluated our experience in a consecutive series of patients undergoing carotid angioplasty and stent placement (CAS). CAS has been introduced recently for treatment of carotid artery stenosis. A major limitation to this modality is the risk of perioperative thromboembolic and ischemic events. To reduce the risk of ischemic complications, abciximab, a platelet glycoprotein IIb/IIIa receptor inhibitor, has been introduced as adjunctive treatment for high-risk patients. METHODS: Each patient was evaluated by a neurologist before, immediately after, and 24 hours after CAS for identification and classification of new neurological deficits. Bleeding events or other complications during hospitalization were recorded. Bleeding complications were classified as major (hemoglobin decrease,g5 g/dl), minor (hemoglobin decrease, 3-5 g/dl), or insignificant. Abciximab was administered intravenously as a single bolus (0.25 mg/kg) and then via infusion (10 microg/min) for 12 hours as an adjunct to CAS in patients considered to be at high risk for thromboembolic events owing to recent ischemic symptoms and/or complex lesion morphology. RESULTS: Intravenously administered abciximab was used in 37 patients (mean age, 70 yr; 21 patients were men) as an adjunct to high-risk CAS. Thirty-three other patients underwent CAS performed with standard intraprocedural heparinization (mean age, 69 yr; 17 patients were men). Minor ischemic strokes were observed in 1 of 37 abciximab-treated patients and in 4 of 33 heparin-treated patients. No major ischemic strokes were observed in either group. Transient neurological deficits were observed in nine patients in the abciximab-treated group and in one patient in the heparin-treated group. Transient neurological deficits in abciximab-treated patients were mainly related to hemodynamic factors (associated with balloon inflation in two patients and with hypotension in another two patients) or occurred after completion of infusion (in three patients). Minor bleeding complications were observed in three patients who received abciximab and in four patients who received standard heparinization. Major bleeding complications were observed in four patients from each group. Two patients who received abciximab developed intracerebral hemorrhages; one hemorrhage was fatal. CONCLUSION: The frequency of ischemic stroke in high-risk patients (3%) with the use of intravenously administered abciximab was lower, but not significantly so, than rates observed in lower-risk patients (12%), although the benefit was lost because of the high rate of intracranial hemorrhages (5%). Further efforts are required to determine appropriate selection criteria for use of intravenously administered abciximab and the effect of other strategies that involve distal protection devices.

Abciximab↗

Aggressive mechanical clot disruption and low-dose intra-arterial third-generation thrombolytic agent for ischemic stroke: a prospective study.

OBJECTIVE: We prospectively evaluated the safety and effectiveness of aggressive mechanical disruption of clot in conjunction with intra-arterial administration of a low-dose third-generation thrombolytic agent (reteplase) to treat ischemic stroke in patients who were considered poor candidates for intravenous alteplase therapy or who failed to improve after intravenous thrombolysis. Mechanical clot disruption was used if low-dose pharmacological thrombolysis was ineffective. This strategy was adopted to increase the recanalization rate without increasing the risk of intracerebral hemorrhage. METHODS: Patients were considered poor candidates for intravenous therapy because of severity of neurological deficits, interval from symptom onset to presentation of at least 3 hours, or recent major surgery. We administered a maximum total dose of 4 U of reteplase intra-arterially in 1-U increments via superselective catheterization. After the initial doses were administered, we performed mechanical angioplasty (for proximal occlusion) or snare manipulation (for distal occlusion) at the occlusion site if recanalization had not occurred. The remaining doses of thrombolytics were subsequently administered if required for further recanalization. Angiographic responses were graded using modified Thrombolysis in Myocardial Infarction (TIMI) criteria. Clinical evaluations were performed before and 24 hours, 7 to 10 days, and 1 to 3 months after treatment. RESULTS: Nineteen consecutive patients were treated (mean age, 64.3 +/- 16.2 yr; 10 were men). Initial National Institutes of Health Stroke Scale scores ranged from 11 to 42. Time from onset to treatment ranged from 1 to 9 hours. Occlusion sites were in the following arteries: cervical internal carotid (n = 7), intracranial internal carotid (n = 1), middle cerebral (n = 9), and basilar (n = 2). Of the 19 patients, thrombolysis alone was used in 5 patients, angioplasty was performed in 11 patients, and snare maneuvers were used in 5 patients. Complete restoration of blood flow (modified TIMI Grade 4) was observed in 12 patients, near-complete restoration of flow (modified TIMI Grade 3) in 4 patients, minimal response (modified TIMI Grade 1) in 1 patient, and no response in 2 patients (modified TIMI Grade 0). Neurological improvement at 24 hours (decline of at least 4 points in National Institutes of Health Stroke Scale score) was observed in seven patients. Five other patients experienced further improvement in National Institutes of Health Stroke Scale score at 7 to 10 days. No vessel rupture, dissection, or symptomatic intracranial hemorrhages were observed. At the time of follow-up evaluation, 7 of 19 patients were functionally independent. CONCLUSION: A high rate of recanalization and clinical improvement can be observed in patients with ischemic stroke using low-dose thrombolytic agents with adjunctive mechanical disruption of clot. Moreover, this strategy may reduce the risk of intracerebral hemorrhage observed with thrombolytics.

Adult↗

Developments in endovascular therapy for acute ischemic stroke.

Treatment for acute ischemic stroke has for years been frustrated by lack of efficacy. Despite a plethora of seemingly promising treatments from animal research, clinical application never came to fruition. Experience seems to indicate that the only truly effective treatment is the rapid restoration of perfusion to ischemic tissue prior to frank infarction. Unfortunately, every agent designed to achieve this goal met with the same ironic limitation; the ability to dissolve clot was coupled with the risk of causing intracerebral hemorrhage. Accordingly, stroke was addressed primarily through modification of risk factors and rehabilitation of the neurological sequelae. However, following the randomized trial of intravenous tissue-type plasminogen activator (t-PA) sponsored by the National Institutes of Neurological Disorders and Stroke (NINDS) in 1995, the first proven effective therapy for acute stroke became available. The door was finally open to emergency treatment of stroke in the acute phase. Moreover, the positive results of the NINDS trial appear to be independent of age. Nevertheless, intravenous thrombolysis remains ineffective in the majority of patients treated and is withheld from an even larger population because of presentation outside of the 3-hour therapeutic window. As a result, effective therapy is not available for most patients presenting with acute stroke. Recent advancements in the evaluation and treatment of acute ischemic stroke, including intra-arterial thrombolysis, mechanical thrombolysis, and combination therapies, hold significant promise for a larger proportion of patients. New imaging technology may also improve our ability to identify patients with viable brain tissue who may derive the greatest benefit from these therapies.

Angioplasty↗

Transradial cerebral angiography: an alternative route.

INTRODUCTION: The transradial approach has been well described for arteriography of the coronary vessels. To assess the safety and success rate of the transradial approach for three-vessel or four-vessel diagnostic cerebral arteriography, we reviewed the experience at our institution and compared our complication rates with those found in the literature for transfemoral cerebral angiography and transradial coronary angiography. METHODS: We reviewed the electronic medical records of 129 consecutive patients in whom 132 cerebral angiographic studies were performed by use of a transradial approach between December 1999 and June 2001. A total of 54 selective catheterizations were performed, of which 39 were of the vertebral artery, 11 of the internal carotid artery, and 4 of the external carotid artery. Records were reviewed for periprocedural and delayed complications, indications for diagnostic angiography, and requirement of conversion to a femoral approach. Records were reviewed prospectively for the first 55 procedures and retrospectively for the next 77 procedures. RESULTS: The mean time to initial clinical follow-up was 1.5 months (median, 0.5 mo). The combined rate of periprocedural and delayed complications was 9%, and there were no major complications. Minor periprocedural complications included transient radial artery spasm (four patients), failure to access the brachial artery (two patients), severe pain (one patient), skin desquamation (one patient), and hematoma (one patient). There were no major complications. At the time of follow-up evaluation, these patients were without deficits related to cannulation of the radial artery. CONCLUSION: The transradial approach for cerebral angiography is a safe alternative to the transfemoral route. After transradial cerebral angiography, patients require a shorter observation period and are not restricted to bed rest. As technological developments generate smaller, more pliable endovascular surgical devices, future endovascular surgery may be performed transradially.

Adolescent↗

Follow-up of stented carotid arteries by Doppler ultrasound.

OBJECTIVE: Blood flow velocity (BFV) in the carotid artery is altered by stent placement. The significance of these alterations is unknown. In our experience, both standard BFV criteria for stenosis and customized criteria recommended by other authors have led to high rates of false-positive studies. We reviewed our experience with Doppler ultrasonography immediately after extracranial carotid artery stent placement to define criteria for restenosis by BFV. METHODS: Complete carotid angiograms and BFV results were available for 114 patients treated between January 1998 and December 1999. Angiographic images obtained immediately after stent placement and at follow-up were measured for residual or recurrent stenosis by a blinded reviewer according to the North American Symptomatic Carotid Endarterectomy Trial method. Results of BFV studies obtained within 1 week of stent placement were interpreted by using two standard criteria (A, peak in-stent systolic velocity greater than 125 cm/s; B, internal carotid artery-to-common carotid artery ratio greater than 3.0) and two customized criteria (C, peak in-stent velocity greater than 170 cm/s; D, internal carotid artery-to-common carotid artery ratio greater than 2.0). The results of follow-up angiography and the most recent Doppler study were compared for nine patients. RESULTS: On the basis of an examination of Doppler studies obtained immediately after stent placement, 36 patients met Criterion A for stenosis according to measured BFV (corresponding mean angiographic stenosis, 14.73 +/- 18.45%), 3 patients met Criterion B (mean stenosis, 1.67 +/- 2.89%), 8 patients met Criterion C (mean stenosis, 12.61 +/- 13.18%), and 14 met Criterion D (mean stenosis, 7.98 +/- 21.74%). No patient with Doppler criteria for significant stenosis had more than 50% residual stenosis. Three of nine patients who underwent follow-up angiography had stenosis of 50% or more; of these three patients, two underwent second angioplasty procedures. The peak in-stent systolic velocity or internal carotid artery-to-common carotid artery BFV ratio for each of the three patients with restenosis, but not for the six other patients, had increased by more than 80% since the immediate post-stenting Doppler study. CONCLUSION: Strict BFV criteria for restenosis after carotid artery stenting are less reliable than change in BFV over time. An immediate post-stenting Doppler study must be obtained to serve as a reference value for future follow-up evaluation.

Aged↗