RESUMEN
INTRODUCTION: Secondary cerebral insults can adversely affect patients with traumatic brain injury. By contrast, the incidence of secondary cerebral insults after aneurysmal subarachnoid hemorrhage (SAH) and their impact on outcome have been less well studied. METHODS: Four hundred and twenty-one patients with SAH who underwent surgical occlusion of their ruptured aneurysm and who received intensive care unit care for ≥48 hours were retrospectively identified from a prospective observational database. Patients were managed according to standard recommendations for SAH. Three secondary cerebral insults were examined: hypotension (<90 mmHg systolic), hypoxia (Pao2 <60 mm Hg), and hyperglycemia (>200 mg/dL). RESULTS: A secondary cerebral insult was observed in 309 (73.4%) patients including 135 (32.1%) who had multiple insults. There was an association between worse clinical grade and development of secondary insults (P = 0.0002), particularly multiple insults (P < 0.0001). When stratified by clinical grade, single (adjusted odds ratio [OR], 2.23; 95% confidence interval [CI], 1.10-4.51; P = 0.026) and multiple (adjusted OR, 4.37; 95% CI, 2.14-8.93; P < 0.0001) secondary cerebral insults were associated with worse outcome. In multivariate analysis and controlling for age, admission clinical grade, severity of SAH on computed tomography, intracerebral hematoma, increased intracranial pressure (>20 mm Hg), rebleed, intraoperative rupture, and hydrocephalus, secondary cerebral insults were independently associated with poor outcome (adjusted OR, 2.45; 95% CI, 1.20-5.02; P = 0.014). CONCLUSIONS: Secondary cerebral insults (hypoxia, hypotension, and hyperglycemia) are common after SAH, including among patients with a good clinical grade. These insults after SAH are associated with worse outcome. These data suggest that prevention of secondary cerebral insults may provide an opportunity to improve patient outcome after SAH.
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Aneurisma Intracraneal/complicaciones , Aneurisma Intracraneal/epidemiología , Hemorragia Subaracnoidea/epidemiología , Hemorragia Subaracnoidea/etiología , Vasoespasmo Intracraneal/etiología , Anciano , Femenino , Escala de Coma de Glasgow , Humanos , Hiperglucemia/etiología , Hipotensión/etiología , Hipoxia/etiología , Incidencia , Aneurisma Intracraneal/cirugía , Modelos Logísticos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Hemorragia Subaracnoidea/cirugía , Vasoespasmo Intracraneal/epidemiologíaRESUMEN
BACKGROUND: The optimal red blood cell transfusion (RBCT) trigger for patients with aneurysmal subarachnoid hemorrhage (SAH) is unknown. In patients with cerebral vasospasm, anemia may increase susceptibility to ischemic injury; conversely, RBCT may worsen outcome given known deleterious effects. OBJECTIVE: To examine the association between RBCT, delayed cerebral ischemia (DCI), vasospasm, and outcome after SAH. METHODS: A total of 421 consecutive patients with SAH, admitted to a neurocritical care unit at a university-affiliated hospital and who underwent surgical occlusion of their ruptured aneurysm were retrospectively identified from a prospective observational database. Propensity score methods were used to reduce the bias associated with treatment selection. RESULTS: Two hundred and sixty-one patients (62.0%) received an RBCT. Angiographic vasospasm (odds ratio [OR] 1.6; 95% confidence interval [CI], 1.1-2.3; P = 0.025) but not severe angiographic spasm, DCI, or delayed infarction was associated with RBCT. A total of 283 patients (67.2%) experienced a favorable outcome, defined as good or moderately disabled on the Glasgow Outcome Scale; 47 (11.2%) were severely disabled or vegetative and 91 patients (21.6%) were dead at 6-month follow-up. Among patients who survived ≥2 days, RBCT was associated with unfavorable outcome (OR, 2.6; 95% CI, 1.6-4.1). Transfusion of ≥3 units of blood was associated with an increased incidence of unfavorable outcome. Propensity analysis to control for the probability of exposure to RBCT conditional on observed covariates measured before RBCT indicates that RBCT is associated with unfavorable outcome in the absence of DCI (OR, 2.17; 95% CI, 1.56-3.01; P < 0.0001) but not when DCI is present (OR, 0.82; 95% CI, 0.35-1.92; P = 0.65). CONCLUSIONS: Blood transfusions are associated with unfavorable outcome after SAH particularly when DCI is absent. Propensity analysis suggests that RBCT may be associated with poor outcome rather than being a marker of disease severity. However, when DCI is present, RBCT may help improve outcome.
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Anemia/terapia , Aneurisma Roto/cirugía , Infarto Cerebral/epidemiología , Transfusión de Eritrocitos/estadística & datos numéricos , Aneurisma Intracraneal/cirugía , Hemorragia Subaracnoidea/cirugía , Vasoespasmo Intracraneal/epidemiología , Adulto , Anciano , Anemia/complicaciones , Aneurisma Roto/complicaciones , Isquemia Encefálica/epidemiología , Angiografía Cerebral , Bases de Datos Factuales , Femenino , Escala de Consecuencias de Glasgow , Humanos , Incidencia , Aneurisma Intracraneal/complicaciones , Masculino , Persona de Mediana Edad , Procedimientos Neuroquirúrgicos , Oportunidad Relativa , Estudios Retrospectivos , Hemorragia Subaracnoidea/etiología , Resultado del TratamientoRESUMEN
OBJECT: The interpretation of intracranial EEG (ICEEG) recordings is a complex balance of the significance of specific rhythms and their relative timing to seizure onset. Ictal and interictal findings are evaluated in light of findings from cortical stimulation of eloquent cortex to determine the area of resection. PATIENTS AND METHODS: Patients with ICEEG electrodes and subsequent surgical resection were retrospectively identified. Only the first 15s of ictal activity, which was divided into five 3-s epochs, was considered. Every electrode in each patient was considered a separate observation in a logistic regression model to predict whether the cortex under a given electrode was included in the planned resection. RESULTS: 19 included patients had a total of 37 unique seizures. Recordings from a total of 1306 electrodes were analyzed. The strongest predictors of resection of cortex underlying a given electrode was the presence of low-voltage fast activity in Epoch 1, rhythmic spikes in Epoch 1, interictal paroxysmal fast activity, and low-voltage fast activity in Epoch 2. High-amplitude beta spikes and rhythmic slow waves were also significant predictors in Epoch 1. Interictal spikes had a higher odds ratio of affecting the planned resection if described as "continuous" or "very frequent". The presence of motor or language cortex were the strongest negative predictors of resecting underlying cortex. CONCLUSIONS: Here we describe a novel model of ictal and interictal patterns significantly associated with the inclusion of cortex underlying a given ICEEG electrode in the surgical resection plan.
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Corteza Cerebral/fisiopatología , Electrocorticografía/métodos , Modelos Estadísticos , Convulsiones/fisiopatología , Convulsiones/cirugía , Adulto , Humanos , Estudios RetrospectivosRESUMEN
Head-of-bed (HOB) elevation is usually restricted in patients with aneurysmal subarachnoid hemorrhage (SAH). The goal of this study is to correlate HOB changes (0° and 90°) with cerebral blood flow using transcranial Doppler (TCD) and thermal diffusion probe in SAH patients. Thirteen patients with SAH were prospectively enrolled in the study. Eight patients underwent placement of a thermal diffusion probe for regional CBF measurement. CBF values were measured with the patients in flat (0°) and upright sitting positions (90°) at days 3, 7, and 10. The average increase in blood flow velocity when changing HOB from 0° to 90° was 7.8% on day 3, 0.1% on day 7, and 13.1% on day 10. The middle cerebral artery had the least changes in velocity. The average regional CBF measurement was 22.7 ± 0.3 mL/100 g/min in the supine position and 23.6 ± 9.1 mg/100 g/min in the sitting position. The changes were not statistically significant. None of the patients developed clinical cerebral vasospasm. Changing HOB position in the setting of SAH did not significantly affect cerebral or regional blood flow. These data suggest that early mobilization should be considered given the detrimental effects of prolonged bed rest.
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Velocidad del Flujo Sanguíneo , Encéfalo/irrigación sanguínea , Circulación Cerebrovascular , Hemorragia Subaracnoidea/patología , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Arteria Cerebral Media/fisiopatología , Hemorragia Subaracnoidea/diagnóstico por imagen , Hemorragia Subaracnoidea/terapia , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Inflammatory cells and molecules may play a critical role in formation and rupture of cerebral aneurysms. Recently, an epidemiologic study reported that acetylsalicylic acid (ASA) decreases the risk of aneurysm rupture. The goal of this study was to determine the effects of ASA on inflammatory cells and molecules in the walls of human cerebral aneurysms, using radiographic and histological techniques. METHODS AND RESULTS: Eleven prospectively enrolled patients harboring unruptured intracranial aneurysms were randomized into an ASA-treated (81 mg daily) group (n=6) and an untreated (control) group (n=5). Aneurysms were imaged at baseline using ferumoxytol-enhanced MRI to estimate uptake by macrophages. After 3 months, patients were reimaged before undergoing microsurgical clipping. Aneurysm tissues were collected for immunostaining with monoclonal antibodies for cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), microsomal prostaglandin E2 synthase-1 (mPGES-1), and macrophages. A decrease in signal intensity on ferumoxytol-enhanced MRI was observed after 3 months of ASA treatment. Expression of COX-2 (but not COX-1), mPGES-1, and macrophages was lower in the ASA group than in the control group. CONCLUSIONS: This study provides preliminary radiographical and histological evidence that ASA may attenuate the inflammatory process in the walls of human cerebral aneurysms. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01710072.
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Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Arterias Cerebrales/efectos de los fármacos , Inflamación/tratamiento farmacológico , Aneurisma Intracraneal/tratamiento farmacológico , Anciano , Angiografía de Substracción Digital , Angiografía Cerebral/métodos , Arterias Cerebrales/inmunología , Arterias Cerebrales/metabolismo , Arterias Cerebrales/patología , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Femenino , Humanos , Inmunohistoquímica , Inflamación/diagnóstico , Inflamación/inmunología , Inflamación/cirugía , Mediadores de Inflamación/metabolismo , Aneurisma Intracraneal/diagnóstico , Aneurisma Intracraneal/inmunología , Aneurisma Intracraneal/cirugía , Oxidorreductasas Intramoleculares/metabolismo , Iowa , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Prostaglandina-E Sintasas , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: The clinical significance of early (ie, within the first 24 hours) uptake of ferumoxytol by macrophages in the wall of human cerebral aneurysms is not clear. The purpose of this study was to determine whether early uptake of ferumoxytol suggests unstable cerebral aneurysm. METHODS: Thirty unruptured aneurysms in 22 patients were imaged with magnetic resonance imaging 24 hours after infusion of ferumoxytol. Eighteen aneurysms were also imaged 72 hours after infusion of ferumoxytol. Aneurysm dome tissue was collected from 4 patients with early magnetic resonance imaging signal changes, 5 patients with late signal changes, and 5 other patients with ruptured aneurysms. The tissue was immunostained for expression of cyclooxygenase-1, cyclooxygenase-2, microsomal prostaglandin E2 synthase-1, and macrophages. RESULTS: In 23% (7/30) of aneurysms, there was pronounced early uptake of ferumoxytol. Four aneurysms were clipped. The remaining 3 aneurysms were managed conservatively; all 3 ruptured within 6 months. In 53% (16 of 30) of aneurysms, there was pronounced uptake of ferumoxytol at 72 hours. Eight aneurysms were surgically clipped, and 8 were managed conservatively; none ruptured or increased in size after 6 months. Expression of cyclooxygenase-2, microsomal prostaglandin E2 synthase-1, and macrophages was similar in unruptured aneurysms with early uptake of ferumoxytol and ruptured aneurysms. Expression of these inflammatory molecules was significantly higher in aneurysms with early uptake of ferumoxytol versus aneurysms with late uptake. CONCLUSIONS: Uptake of ferumoxytol in aneurysm walls within the first 24 hours strongly suggests aneurysm instability and probability of rupture within 6 months, and may warrant urgent intervention.
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Aneurisma Roto/patología , Óxido Ferrosoférrico , Aneurisma Intracraneal/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Aneurisma Roto/metabolismo , Ciclooxigenasa 1/metabolismo , Ciclooxigenasa 2/metabolismo , Progresión de la Enfermedad , Diagnóstico Precoz , Femenino , Estudios de Seguimiento , Hematínicos , Humanos , Aneurisma Intracraneal/metabolismo , Oxidorreductasas Intramoleculares/metabolismo , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Prostaglandina-E SintasasRESUMEN
BACKGROUND AND PURPOSE: Cyclooxygenase-2 (COX-2) and Microsomal Prostaglandin E2 Synthase-1 (mPGES-1) catalyze isomerization of the cyclooxygenase product PGH2 into PGE2. Deletion of COX-2/mPGES-1 suppresses carotid artery atherogenesis and angiotensin II-induced aortic aneurysms formation, and attenuates neointimal hyperplasia after vascular injury in mice. The upregulation of COX-2/mPGES-1 in the wall of ruptured human cerebral aneurysms is not known. METHODS: Ten patients with intracranial aneurysms (5 ruptured and 5 nonruptured) underwent microsurgical clipping. During the procedure, a segment of the aneurysm dome was resected and immunostained with monoclonal antibodies for COX-1, COX-2, and mPGES-1. A segment of the superficial temporal artery was also removed and immunostained with monoclonal antibodies for COX-1, COX-2, and mPGES-1. RESULTS: All 10 aneurysm tissues stained positive for mPGES-1 monoclonal antibody. Expression of mPGES-1 was more abundant in ruptured aneurysm tissue than in nonruptured aneurysms, based on a semiquantitative grading. None of the superficial temporal artery specimens expressed mPGES-1. COX-2 was upregulated in the same distribution as was mPGES-1. COX-1 was present constitutively in all tissues. CONCLUSIONS: COX-2/mPGES-1 are expressed in the wall of human cerebral aneurysms and more abundantly so in ruptured aneurysms than in nonruptured. We speculate that the protective effect of aspirin against rupture of cerebral aneurysms may be mediated in part by inhibition of COX-2/mPGES-1.
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Aneurisma Roto/enzimología , Ciclooxigenasa 2/biosíntesis , Aneurisma Intracraneal/enzimología , Oxidorreductasas Intramoleculares/biosíntesis , Microsomas/enzimología , Regulación hacia Arriba/fisiología , Adulto , Anciano , Aneurisma Roto/patología , Femenino , Humanos , Aneurisma Intracraneal/patología , Masculino , Microsomas/patología , Persona de Mediana Edad , Prostaglandina-E SintasasRESUMEN
OBJECTIVE: Macrophages play a critical role in cerebral aneurysm formation and rupture. The purpose of this study is to demonstrate the feasibility and optimal parameters of imaging macrophages within human cerebral aneurysm wall using ferumoxytol-enhanced MRI. METHODS AND RESULTS: Nineteen unruptured aneurysms in 11 patients were imaged using T2*-GE-MRI sequence. Two protocols were used. Protocol A was an infusion of 2.5 mg/kg of ferumoxytol and imaging at day 0 and 1. Protocol B was an infusion of 5 mg/kg of ferumoxytol and imaging at day 0 and 3. All images were reviewed independently by 2 neuroradiologists to assess for ferumoxytol-associated loss of MRI signal intensity within aneurysm wall. Aneurysm tissue was harvested for histological analysis. Fifty percent (5/10) of aneurysms in protocol A showed ferumoxytol-associated signal changes in aneurysm walls compared to 78% (7/9) of aneurysms in protocol B. Aneurysm tissue harvested from patients infused with ferumoxytol stained positive for both CD68+, demonstrating macrophage infiltration, and Prussian blue, demonstrating uptake of iron particles. Tissue harvested from controls stained positive for CD68 but not Prussian blue. CONCLUSIONS: Imaging with T2*-GE-MRI at 72 hours postinfusion of 5 mg/kg of ferumoxytol establishes a valid and useful approximation of optimal dose and timing parameters for macrophages imaging within aneurysm wall. Further studies are needed to correlate these imaging findings with risk of intracranial aneurysm rupture.
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Óxido Ferrosoférrico , Aneurisma Intracraneal/patología , Macrófagos/patología , Imagen por Resonancia Magnética , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Biomarcadores/metabolismo , Colorantes , Medios de Contraste , Estudios de Factibilidad , Femenino , Ferrocianuros , Humanos , Inmunohistoquímica , Aneurisma Intracraneal/inmunología , Iowa , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Valor Predictivo de las Pruebas , Estudios Prospectivos , Reproducibilidad de los Resultados , Coloración y Etiquetado/métodos , Factores de TiempoRESUMEN
BACKGROUND: Interhospital transfer of patients with intracranial hemorrhage can offer improved care, but may be associated with complications. METHODS: A prospective single-center study was conducted between 2/2008 and 6/2010 of patients with subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH) and subdural hemorrhage (SDH), admitted to the neuro-ICU at a tertiary-care academic hospital. Admission demographics, complications and 3-month functional outcomes were compared between directly admitted and transferred patients. The effect of transfer time on complications and outcomes was assessed. RESULTS: Of 257 total patients, 120 (47%) were transferred and 137 (53%) were directly admitted. About 86 (34%) had SAH, 80 (31%) had ICH and 91 (35%) had SDH. The median transfer time was 190 min (46-1,446). Transferred patients were significantly less educated, less likely to be insured and more frequently had SAH as a diagnosis than directly admitted patients (all P < 0.05), though admission neurological and cognitive status was similar. Complications did not differ between transferred and directly admitted patients; however, among transferred patients, longer transfer time was associated with aneurysm rebleed (7.3 vs. 1.8%, P = 0.007) and tracheostomy (20 vs. 17.5%, P = 0.013). In multivariate analysis, after adjusting for other predictors, transferred patients had worse cognitive outcome at 3-months (adjusted OR 12.4, 95% CI 1.2-125.2, P = 0.033) compared to direct admits, though there were no differences in death, disability or length of stay (LOS). CONCLUSIONS: Transferred patients had similar rates of death, disability and LOS as directly admitted patients, though worse 3-month cognitive outcomes. Prolonged time to interhospital transfer was associated with an increased risk of aneurysm rerupture and tracheostomy.
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Hemorragias Intracraneales/mortalidad , Hemorragias Intracraneales/terapia , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Transferencia de Pacientes/estadística & datos numéricos , Centros de Atención Terciaria/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crítica/mortalidad , Evaluación de la Discapacidad , Femenino , Hematoma Subdural/mortalidad , Hematoma Subdural/rehabilitación , Hematoma Subdural/terapia , Mortalidad Hospitalaria , Humanos , Incidencia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Hemorragias Intracraneales/rehabilitación , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Hemorragia Subaracnoidea/mortalidad , Hemorragia Subaracnoidea/rehabilitación , Hemorragia Subaracnoidea/terapia , Adulto JovenRESUMEN
In the present review (part II), we discuss the challenges and promises of selective drug delivery to ischemic brain tissue by liposome technologies. In part I of this serial review, we proposed "selective drug delivery to ischemic brain tissue" as a technique for neuroprotective treatment of acute ischemic stroke. To be effective, drugs must pass a series of barriers to arrive at ischemic brain. Brain ischemia results in metabolic and structural changes in the ischemic region, which cause additional obstacles for drug delivery. Liposome drug delivery system can pass these barriers and selectively target ischemic tissue by utilizing ischemia-induced changes in metabolism and molecular structure.
RESUMEN
OBJECTIVES: the frequency and predictors of recurrent symptomatic and angiographic vasospasm after angioplasty or intra-arterial chemical vasodilatation (IACV) in patients with subarachnoid hemorrhage (SAH) are not well characterized. METHODS: a retrospective review of serial clinical and angiographic data was conducted between 7/2001-6/2008 on spontaneous SAH patients who underwent endovascular therapy for symptomatic vasospasm. RESULTS: of 318 SAH patients, symptomatic vasospasm occurred in 80 (25%) and endovascular intervention was performed on 69 (22%) patients. Of these 69 patients, all received IACV in 274 vessels and 33 also underwent angioplasty in a total of 76 vessels. Recurrent angiographic vasospasm occurred in the same vessel segment in 9/23 (39%) patients who received both angioplasty + IACV compared to 40/49 (82%) of patients who received IACV alone (P < 0.001). Recurrent symptomatic vasospasm occurred in 10/26 (38%) angioplasty + IACV patients compared to 28/37 (76%) patients who received IACV alone (P = 0.003). The modified-Fisher Score, A1 spasm, distal and multi-vessel vasospasm predicted recurrent angiographic spasm after IACV alone (P < 0.05). Procedural complications occurred in 4% of IACV alone patients and 6% of angioplasty + IACV patients (P = 0.599). CONCLUSIONS: recurrent angiographic or symptomatic vasospasm is not uncommon after angioplasty + IACV, but appears to occur significantly less than after IACV alone, without any increase in procedural complications.
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Procedimientos Endovasculares/efectos adversos , Hemorragia Subaracnoidea/cirugía , Vasoespasmo Intracraneal/etiología , Adulto , Anciano , Anciano de 80 o más Años , Angiografía/métodos , Distribución de Chi-Cuadrado , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud/métodos , Recurrencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Hemorragia Subaracnoidea/complicaciones , Tomógrafos Computarizados por Rayos X , Vasoespasmo Intracraneal/diagnóstico por imagenRESUMEN
Penumbra is the viable tissue around the irreversibly damaged ischemic core. The purpose of acute stroke treatment is to salvage penumbral tissue and to improve brain function. However, the majority of acute stroke patients who have treatable penumbra are left untreated. Therefore, developing an effective non-recanalizational therapeutics, such as neuroprotective agents, has significant clinical applications. Part I of this serial review on "targeting penumbra" puts special emphases on penumbral pathophysiology and the development of therapeutic strategies. Bioenergetic intervention by massive metabolic suppression and direct energy delivery would be a promising future direction. An effective drug delivery system for this purpose should be able to penetrate BBB and achieve high local tissue drug levels while non-ischemic region being largely unaffected. Selective drug delivery to ischemic stroke penumbra is feasible and deserves intensive research.
RESUMEN
Brain tissue oxygenation affects cerebral function and blood flow (CBF). Adenosine (Ado), a purine nucleoside, moderates neuronal activity, and arterial diameter. The cellular source of Ado in brain remains elusive; however, astrocytes are a logical site of production. Using astrocytic cultures, we tested the hypothesis that astrocytic derived Ado reflects cerebral oxygenation. We found that during alterations in pO(2), extracellular levels of Ado [Ado](e) changed rapidly. Graded reductions of oxygen tension revealed that[Ado](e) reached 10(-7) M to 10(-6) M with a pO(2) of 30-10mmHg, comparable with [Ado](e) and oxygen levels found in brain tissue during normoxemia. Higher O(2) levels were associated with a depression of [Ado](e). Under conditions of low pO(2) (pO(2) Asunto(s)
Adenosina/metabolismo
, Astrocitos/citología
, Astrocitos/metabolismo
, Corteza Cerebral/metabolismo
, Consumo de Oxígeno/fisiología
, Oxígeno/metabolismo
, Nucleótidos de Adenina/metabolismo
, Nucleótidos de Adenina/fisiología
, Adenosina/biosíntesis
, Animales
, Astrocitos/efectos de los fármacos
, Técnicas de Cultivo de Célula
, Células Cultivadas
, Corteza Cerebral/citología
, Corteza Cerebral/patología
, Líquido Extracelular/metabolismo
, Hipoxantina/metabolismo
, Hipoxia Encefálica/metabolismo
, Hipoxia Encefálica/patología
, Inosina/metabolismo
, Ratas
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OBJECTIVE: Carotid artery angioplasty and carotid artery stenting (CAS) offer a viable alternative to carotid endarterectomy for symptomatic and asymptomatic patients; however, the complication rates associated with CAS may be higher than previously documented. We evaluated the safety and efficacy of CAS in high surgical risk patients in a single neurovascular center retrospective review. METHODS: An institutional review board-approved retrospective review of the clinical variables and treatment outcomes of 101 consecutive patients (109 stents) from July 2001 to March 2007 with carotid stenosis were analyzed. Both symptomatic and asymptomatic stenoses were studied in high surgical risk patients as defined by the SAPPHIRE (Stenting and Angioplasty with Protection in Patients at High-Risk for Endarterectomy) trial. Specifically, those patients with clinically significant cardiac disease (congestive heart failure, abnormal stress test, or need for open-heart surgery), severe pulmonary disease, contralateral carotid occlusion, contralateral laryngeal nerve palsy, recurrent stenosis after carotid endarterectomy, previous radical neck surgery, or radiation therapy to the neck, and an age older than 80. RESULTS: Seventy-four percent of the patients were symptomatic (n = 81), and the mean stenosis in symptomatic patients was 83%. Reasons for stenting included cardiac/pulmonary/medical risk (60%), contralateral internal carotid artery occlusion (8%), recurrent stenosis after carotid endarterectomy (11%), carotid dissection (6%), age older than 80 (7%), previous radical neck surgery (7%), and previous neck radiation (1%). Stent deployment was achieved in 108 of 109 vessels (99%). Distal embolic protection devices were used in 72% of cases treated. The overall rate of in-hospital adverse events (transient ischemic attack, intracranial hemorrhage, minor stroke, major stroke, myocardial infarction, and death) was 8.3% (9 of 109). Of these events, 2 patients (1.8%) experienced a hemispheric transient ischemic attack (neurological symptoms that resolved within 24 hours), 2 others (1.8%) had transiently symptomatic acute reperfusion syndrome. The 30-day stroke/death/myocardial infarction risk was 4.6% (n = 5). Of these patients, 3 had minor strokes (2.7%) defined as a modified Rankin Scale score less than 3 at 1-year follow-up, 1 had a major stroke (0.9%) defined as a modified Rankin Scale score of 3 or more at 1-year follow-up, and 1 patient died after a periprocedural myocardial infarction (0.9%). CONCLUSION: CAS can be performed with a low 30-day complication rate, even with a higher percentage of symptomatic lesions. The results support the use of CAS in high surgical risk patients with both significant symptomatic and asymptomatic carotid artery disease.
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Estenosis Carotídea/cirugía , Endarterectomía Carotidea/métodos , Resultado del Tratamiento , Angioplastia/métodos , Arterias Carótidas/cirugía , Estenosis Carotídea/patología , Estenosis Carotídea/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: Red blood cell transfusion (RBCT) is associated with medical complications in general medical and surgical patients. We examined the hypothesis that RBCT during intensive care unit (ICU) care is associated with medical complications after subarachnoid hemorrhage (SAH). METHODS: We retrospectively analyzed a prospective observational database containing 421 patients with SAH (mean age, 51.5 years; standard deviation, 14.6 years). Logistic regression models were used to adjust for age, admission hemoglobin (Hgb), clinical grade, average ICU Hgb, and symptomatic vasospasm. RESULTS: Two hundred fourteen patients received an RBCT during their ICU stay. Medical complications were identified in 156 patients and were more common in those who received blood (46%) than in those who did not (29.8%) (P < .001). Major medical complications (cardiac, pulmonary, renal, or hepatic) occurred in 111 patients, and minor complications (eg, skin rash, deep vein thrombosis) occurred in 45 patients. Any non-central nervous system infection (n = 183; P < .001), including pneumonia (n = 103; P < .001) or septicemia (n = 36; P = .02), was more common with RBCT. Central nervous system infections (meningitis, cranial wound, n = 15) also were associated with RBCT (P = .03). Mechanically ventilated patients (n = 259) were more likely to have received an RBCT than those who did not (P < .001). When logistic regression was used to control for age, admission clinical grade and Hgb, average ICU Hgb, symptomatic vasospasm, and other admission variables associated with outcome, the following factors (odds ratio; 95% confidence interval) were associated with RBCT: any medical complication (1.8; 1.1-3.0), major medical complications (2.1; 1.2-3.7), any infection (2.8; 1.7-4.5), pneumonia (2.6; 1.5-4.7), septicemia (2.9; 1.2-6.8), and need for mechanical ventilation (2.8; 1.5-5.1). CONCLUSION: These data suggest that RBCTs are associated with medical complications after SAH. However, the data do not infer causation, and further study is necessary to better define the indications for transfusion after SAH.
Asunto(s)
Transfusión de Eritrocitos/efectos adversos , Infecciones/etiología , Hemorragia Subaracnoidea/terapia , Adulto , Anciano , Angiografía Cerebral/métodos , Cuidados Críticos , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Complicaciones Posoperatorias , Estudios Prospectivos , Estudios Retrospectivos , Medición de Riesgo , Succión/métodos , Tomografía Computarizada de Emisión/métodos , Vasoespasmo Intracraneal/etiologíaRESUMEN
OBJECT: Vasospasm is a leading cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). It is important to predict which patients are at risk for vasospasm so that interventions can be made. There are several potential risk factors for vasospasm, one of which is age. However, the effect of age on vasospasm, particularly symptomatic vasospasm, remains controversial. METHODS: Three hundred ninety-one patients were retrospectively identified from a prospective observational database of patients with SAH who had been admitted to a single center. Demographic and clinical data were recorded, and cerebral angiograms obtained at admission and between 5 and 10 days later were compared. The relationship between age and angiographic and symptomatic vasospasms was examined using logistic regression techniques. RESULTS: Mild (86 patients), moderate (69 patients), severe (56 patients), and no angiographic vasospasms (180 patients) were documented by comparing admission and follow-up angiograms in each patient. Symptomatic vasospasm was identified in 69 patients (17.6%). Angiographic vasospasm was more frequent as age decreased. Except in patients < 30 years old, the frequency of symptomatic vasospasm also increased with decreasing age (p = 0.0001). After adjusting for variables known to be associated with vasospasm, an advanced age was associated with a reduced incidence of any angiographic vasospasm (OR 0.96, 95% CI 0.94-0.97), severe angiographic vasospasm (OR 0.96, 95% CI 0.95-0.98), and symptomatic vasospasm (OR 0.98, 95% CI 0.96-0.99). CONCLUSIONS: Results in this study show that a younger age is associated with an increased incidence of angiographic and symptomatic vasospasm.
Asunto(s)
Angiografía Cerebral , Examen Neurológico , Hemorragia Subaracnoidea/diagnóstico por imagen , Vasoespasmo Intracraneal/diagnóstico por imagen , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Factores de Riesgo , Hemorragia Subaracnoidea/mortalidad , Tasa de Supervivencia , Vasoespasmo Intracraneal/mortalidadRESUMEN
OBJECT: The role of adenosine A(2A) receptors in the early vascular response after subarachnoid hemorrhage (SAH) is unknown. In other forms of cerebral ischemia both activation and inhibition of A(2A) receptors is reported to be beneficial. However, these studies mainly used pharmacological receptor modulation, and most of the agents available exhibit low specificity. The authors used adenosine A(2A) receptor knockout mice to study the role of A(2A) receptors in the early vascular response to SAH. METHODS: Subarachnoid hemorrhage was induced in wild-type mice (C57BL/6) and A(2A) receptor knockout mice by endovascular puncture. Cerebral blood flow, intracranial pressure, and blood pressure were recorded, and cerebral perfusion pressure was deduced. Animals were sacrificed at 1, 3, or 6 hours after SAH or sham surgery. Coronal brain sections were immunostained for Type IV collagen, the major protein of the basal lamina. The internal diameter of major cerebral arteries and the area fraction of Type IV collagen-positive microvessels (< 100 µm) were determined. RESULTS: The initial increase in intracranial pressure and decrease in cerebral perfusion pressure at SAH induction was similar in both types of mice, but cerebral blood flow decline was significantly smaller in A(2A) receptor knockout mice as compared with wild-type cohorts. The internal diameter of major cerebral vessels decreased progressively after SAH. The extent of diameter reduction was significantly less in A(2A) receptor knockout mice than in wild-type mice. Type IV collagen immunostaining decreased progressively after SAH. This decrease was significantly less in A(2A) receptor knockout mice than in wild-type mice. CONCLUSIONS: These results demonstrate that global inactivation of A(2A) receptors decreases the intensity of the early vascular response to SAH. Early inhibition of A(2A) receptors after SAH might reduce cerebral injury.
Asunto(s)
Isquemia Encefálica/metabolismo , Receptor de Adenosina A2A/metabolismo , Hemorragia Subaracnoidea/metabolismo , Animales , Análisis de los Gases de la Sangre , Presión Sanguínea/fisiología , Encéfalo/patología , Isquemia Encefálica/patología , Capilares/metabolismo , Capilares/patología , Arterias Cerebrales/metabolismo , Arterias Cerebrales/patología , Circulación Cerebrovascular/fisiología , Colágeno Tipo IV/metabolismo , Técnica del Anticuerpo Fluorescente , Presión Intracraneal/fisiología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor de Adenosina A2A/genética , Hemorragia Subaracnoidea/patologíaRESUMEN
The mechanisms responsible for vascular autoregulation in the brain during changes in mean arterial blood pressure are ambiguous. Potentially, adenosine, a purine nucleoside and potent vasodilator, may be involved as earlier studies have documented an increase in brain adenosine concentrations with cerebral ischemia and hypotension. Consequently, we tested the hypothesis that adenosine is involved in vasodilatation during hypotension within the autoregulatory range (>50 mm Hg) by exposing adenosine 2a receptor (A2aR) knockout and wild type (WT) mice to short (2 to 5 mins) periods of hypotension. We found that autoregulation was significantly (P<0.05) impaired by 29% in A2a knockout mice as compared with WT animals. Furthermore, the A2R antagonist (A2a>A2b:10-85>1), ZM-241385, in a dose (1, 5, 10 mg/kg, intraperitoneally)-related manner, attenuated autoregulation in WT mice. In knockout mice treated with ZM-2413585 (5 and 10 mg/kg), autoregulation was further impaired indicating that A2b receptors also participated in cerebral vasodilatation. Treatment with dipyridamole (1.0 mg/kg) that increases extracellular concentrations of adenosine improved autoregulation in the A2aR knockout mice. We would conclude that adenosine through both A2a and A2b receptors is involved in physiologic vascular regulation during hypotension even within the autoregulatory range.
Asunto(s)
Circulación Cerebrovascular/fisiología , Hipotensión/inducido químicamente , Receptor de Adenosina A2A/metabolismo , Receptor de Adenosina A2B/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismo , Antagonistas del Receptor de Adenosina A2 , Animales , Antihipertensivos/metabolismo , Presión Sanguínea/fisiología , Dipiridamol/metabolismo , Masculino , Ratones , Ratones Noqueados , Fenetilaminas/metabolismo , Receptor de Adenosina A2A/genética , Triazinas/metabolismo , Triazoles/metabolismo , Vasodilatación/fisiología , Vasodilatadores/metabolismoRESUMEN
OBJECT: Cerebrovascular dysfunction after subarachnoid hemorrhage (SAH) may contribute to ischemia, but little is known about the contribution of intracerebral arterioles. In this study, the authors tested the hypothesis that SAH inhibits the vascular reactivity of intracerebral arterioles and documented the time course of this dysfunction. METHODS: Subarachnoid hemorrhage was induced using an endovascular filament model in halothane-anesthetized male Sprague-Dawley rats. Penetrating intracerebral arterioles were harvested 2, 4, 7, or 14 days postinsult, cannulated using a micropipette system that allowed luminal perfusion and control of luminal pressure, and evaluated for reactivity to vasodilator agents. RESULTS: Spontaneous tone developed in all pressurized (60 mm Hg) intracerebral arterioles harvested in this study (from 66 rats), with similar results in the sham and SAH groups. Subarachnoid hemorrhage did not affect dilation responses to acidic pH (6.8) but led to a persistent impairment of endothelium-dependent dilation responses to adenosine triphosphate (p < 0.01), as well as a transient attenuation (p < 0.05) of vascular smooth muscle-dependent dilation responses to adenosine, sodium nitroprusside, and 8-Br-cyclic guanosine monophosphate (cGMP). Impairment of NO-mediated dilation was more sustained than adenosine- and 8-Br-cGMP-induced responses (up to 7 days postinsult compared with 2 days). All smooth muscle-dependent responses returned to sham levels by 14 days after SAH. CONCLUSIONS: Subarachnoid hemorrhage led to a persistent impairment of endothelium-dependent dilation and a transient attenuation of vascular smooth muscle-dependent dilation responses to adenosine. Impairment of NO-mediated dilation occurred when the response to cGMP was intact, suggesting a change in cGMP levels rather than an alteration in intracellular mechanisms downstream from cGMP.