RESUMO
PURPOSE: Stereotactic radiosurgery (SRS) is an evolving modality for treating well-circumscribed intracranial lesions. Different physical methods have been developed to deliver highly localized dose distributions accurately. We review the different methods and the documented clinical results to present a coherent view of radiosurgery, and to aid physicians and physicists in the appropriate use of this modality. DESIGN: A review of the medical physics and clinical literature was conducted. The physical aspects of the different methods and their impact on treatment were summarized. Results were compiled from those individual clinical series with adequate follow-up data to compare the various modalities with respect to treatment outcome for benign tumors, metastases, and vascular malformations. RESULTS: The physical accuracy was comparable between radiosurgical methods. Differences between gamma radiation and linear accelerator methods had little effect on the dose distribution for single isocenter treatments. Charged particle methods could produce better dose localization for large lesions (> 25 cm3) than was possible with photon methods. Clinical results indicate similar lesion control rates between all radiosurgical methods. There was a progressive increase in the median size of treated lesions for gamma radiation, linear accelerator, and charged particle methods. CONCLUSION: For small lesions (< 5 cm3), physical dose distributions are similar for the photon methods, but linear accelerator methods offer more flexibility for the treatment of intermediate-sized (5 to 25 cm3) lesions in applying future technical developments. More clinical results are needed before firm conclusions can be drawn on the type of lesions to be treated, and the dose-volume parameters to be used.
Assuntos
Radiocirurgia/métodos , Neoplasias Encefálicas/cirurgia , Raios gama , Humanos , Malformações Arteriovenosas Intracranianas/cirurgia , Aceleradores de Partículas , Hipófise/cirurgia , Radiocirurgia/instrumentaçãoRESUMO
BACKGROUND AND PURPOSE: Carotid endarterectomy (CEA) reduces the risk of stroke ipsilateral to recently symptomatic severe carotid stenosis. Other techniques such as percutaneous transluminal angioplasty with stenting are currently being compared with CEA. Thus far, case series and several small, randomized, controlled trials of CEA versus percutaneous transluminal angioplasty (with and without stenting) have focused primarily on the 30-day procedural risks of stroke and death. However, long-term durability is also important. To determine the long-term risk of stroke after CEA and to identify risk factors, we studied patients in the European Carotid Study Trial (ECST), the largest published cohort with long-term follow-up by physicians after CEA. METHODS: Risks of ipsilateral carotid territory ischemic stroke were calculated by Kaplan-Meier analysis starting on the 30th day after CEA in 1728 patients who underwent trial surgery. Risk factors were determined by Cox regression. For comparison, we also determined the "background" risk of stroke on medical treatment in the ECST in the territory of 558 previously asymptomatic contralateral carotid arteries with <30% angiographic stenosis (ECST method) at randomization. RESULTS: The risks of disabling ipsilateral ischemic stroke and any ipsilateral ischemic stroke were constant after CEA, reaching 4.4% [95% confidence interval (CI), 3.0 to 5.8] and 9.7% (95% CI, 7.6 to 11.7), respectively, by 10 years. The equivalent ischemic stroke risks distal to contralateral <30% asymptomatic carotid stenoses were 1.9% (95% CI, 0.8 to 3.2) and 4.5% (95% CI, 1.5 to 7.4). Presentation with cerebral symptoms, diabetes, elevated systolic blood pressure, smoking, male sex, increasing age, and a lesser severity of preoperative stenosis were associated with an increased risk of late stroke after CEA, but plaque morphology and patch grafting were not. CONCLUSIONS: Although the risk of late ipsilateral ischemic stroke after CEA for symptomatic stenosis is approximately double the background risk in the territory of <30% asymptomatic stenosis, it is still only approximately 1% per year and remains low for at least 10 years after CEA. This is the standard against which alternative treatments should be judged. Several risk factors may be useful in identifying patients at particularly high risk of late postoperative stroke.
Assuntos
Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/estatística & dados numéricos , Complicações Pós-Operatórias , Acidente Vascular Cerebral/etiologia , Estenose das Carótidas/epidemiologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Estudos de Coortes , Europa (Continente) , Feminino , Seguimentos , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Modelos de Riscos Proporcionais , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Análise de Sobrevida , Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Hypothermia is effective in improving outcome in experimental models of brain infarction. We studied the feasibility and safety of hypothermia in patients with acute ischemic stroke treated with thrombolysis. METHODS: An open study design was used. All patients presented with major ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score >15) within 6 hours of onset. After informed consent, patients with a persistent NIHSS score of >8 were treated with hypothermia to 32+/-1 degrees C for 12 to 72 hours depending on vessel patency. All patients were monitored in the neurocritical care unit for complications. A modified Rankin Scale was measured at 90 days and compared with concurrent controls. RESULTS: Ten patients with a mean age of 71.1+/-14.3 years and an NIHSS score of 19.8+/-3.3 were treated with hypothermia. Nine patients served as concurrent controls. The mean time from symptom onset to thrombolysis was 3.1+/-1.4 hours and from symptom onset to initiation of hypothermia was 6.2+/-1.3 hours. The mean duration of hypothermia was 47.4+/-20.4 hours. Target temperature was achieved in 3.5+/-1.5 hours. Noncritical complications in hypothermia patients included bradycardia (n=5), ventricular ectopy (n=3), hypotension (n=3), melena (n=2), fever after rewarming (n=3), and infections (n=4). Four patients with chronic atrial fibrillation developed rapid ventricular rate, which was noncritical in 2 and critical in 2 patients. Three patients had myocardial infarctions without sequelae. There were 3 deaths in patients undergoing hypothermia. The mean modified Rankin Scale score at 3 months in hypothermia patients was 3.1+/-2.3. CONCLUSION: Induced hypothermia appears feasible and safe in patients with acute ischemic stroke even after thrombolysis. Refinements of the cooling process, optimal target temperature, duration of therapy, and, most important, clinical efficacy, require further study.
Assuntos
Isquemia Encefálica/terapia , Hipotermia Induzida , Acidente Vascular Cerebral/terapia , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Bradicardia/etiologia , Bradicardia/genética , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico , Angiografia Cerebral , Estudos de Viabilidade , Feminino , Febre/etiologia , Fibrinolíticos/uso terapêutico , Humanos , Hipotensão/etiologia , Hipotermia Induzida/efeitos adversos , Hipotermia Induzida/mortalidade , Infecções/etiologia , Masculino , Melena/etiologia , Pessoa de Meia-Idade , Monitorização Fisiológica , Infarto do Miocárdio/etiologia , Projetos Piloto , Índice de Gravidade de Doença , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler Transcraniana , Complexos Ventriculares Prematuros/etiologiaRESUMO
We studied the influences of sympathetic and cholinergic mechanisms on pial arteriolar responses during cortical activation in the rat. Adult male Sprague-Dawley rats were anesthetized with alpha-chloralose and urethane and mechanically ventilated. Pial arterioles on the somatosensory cortex were visualized on a video monitor through a closed cranial window. Changes in arteriolar diameter induced by sciatic nerve stimulation (0.2 V, 5 Hz, 5 ms, for 20 s) were measured before and after (a) ipsilateral superior cervical ganglionectomy (n = 5), (b) intravenous (0.5 mg/kg) administration and topical (10(-5) M) application of atropine (n = 5), and (c) lesion of the nucleus basalis magnocellularis (the major source of intracerebral acetylcholine neurons, n = 7). Unilateral nucleus basalis magnocellularis lesions were performed stereotactically by injection of ibotenic acid (25 nmol/microliter). Sensory cortex cholinergic denervation was confirmed histologically. These treatments had no significant effect on arteriolar responses to sciatic nerve stimulation. Thus, the present results suggest that neither sympathetic nor cholinergic mechanisms play a significant role in somatosensory evoked cerebral vasodilation.
Assuntos
Encéfalo/irrigação sanguínea , Colina/fisiologia , Nervo Isquiático/fisiologia , Sistema Nervoso Simpático/fisiologia , Vasodilatação , Animais , Arteríolas/inervação , Arteríolas/fisiologia , Atropina/farmacologia , Estimulação Elétrica , Gânglios Simpáticos/fisiologia , Gânglios Simpáticos/cirurgia , Ganglionectomia , Ácido Ibotênico/farmacologia , Masculino , Núcleo Olivar/efeitos dos fármacos , Núcleo Olivar/fisiologia , Pia-Máter/irrigação sanguínea , Ratos , Ratos EndogâmicosRESUMO
Anatomical and clinical observations suggest that supratentorial vascular structures contain afferent projections from the trigeminal ganglia. To characterize this innervation, horseradish peroxidase (HRP) and HRP conjugated to wheat germ agglutinin were applied to the pial and dural arteries and sinuses of 33 cats. HRP was restricted to the site of interest by applying it dissolved in a viscous polymer, polyvinyl alcohol (PVA), to achieve slow release and minimize diffusion. The ganglia of cranial nerves V, VII, IX, and X and the superior cervical ganglia (SCGs) were examined bilaterally for the presence of retrogradely transported protein. Horseradish peroxidase applied to the proximal middle cerebral artery was located in cell bodies occupying the portion of the ipsilateral trigeminal ganglion corresponding to the ophthalmic division and throughout both SCGs. When the tracer was applied to the right anterior or posterior superior sagittal sinus, HRP-positive cells were present as above, predominantly in the ipsilateral trigeminal ganglia corresponding to the ophthalmic division and throughout both SCG. When applied to the right middle meningeal artery, HRP was observed within neurons of ipsilateral SCG and in the ophthalmic division of trigeminal ganglia; a few enzyme-containing cells were present in ipsilateral regions corresponding to the second and third divisions. These observations support the concept that supratentorial vascular structures receive afferent nervous projections from trigeminal neurons.
Assuntos
Circulação Cerebrovascular , Dura-Máter/irrigação sanguínea , Pia-Máter/irrigação sanguínea , Nervo Trigêmeo/anatomia & histologia , Vias Aferentes/anatomia & histologia , Animais , Transporte Axonal , Gatos , Peroxidase do Rábano Silvestre , Fluxo Sanguíneo Regional , Gânglio Trigeminal/anatomia & histologiaRESUMO
PURPOSE: Prior work in our laboratory demonstrated that external gamma irradiation administered within 48 h following balloon catheter carotid artery injury in rats produced a marked inhibition of intimal hyperplasia and restenosis. The current study used smooth muscle cells (SMC) in vitro to examine the radiation dose response and to investigate the cellular mechanism by which radiation inhibits SMC proliferation. METHODS AND MATERIALS: Quiescent rat aortic SMC in plasma were refed with whole blood serum to stimulate synchronous proliferation and immediately irradiated with single fraction doses of 1.25-20 Gy. RESULTS: Comparison between a micronucleus assay and a clonogenic assay indicated a dose-dependent inhibition of SMC growth, with an ED50 at 2-3 Gy. The micronucleus assay also demonstrated a dose-dependent increase in apparent chromosomal damage at 72 h after irradiation. Inhibition of SMC growth by radiation did not correlate with changes in intracellular or released mitogenic activity. Furthermore, there was no evidence of apoptosis in irradiated SMC up to 96 h after treatment. CONCLUSION: Radiation likely inhibits SMC proliferation after arterial injury by a dose-dependent mechanism of lethal and/or sublethal cellular injury leading to clonogenic cell death.
Assuntos
Músculo Liso Vascular/efeitos da radiação , Animais , Apoptose , Divisão Celular/efeitos da radiação , Ensaio de Unidades Formadoras de Colônias , Meios de Cultura , DNA/análise , Relação Dose-Resposta à Radiação , Testes para Micronúcleos , Mitógenos/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , RatosRESUMO
The potential role of radiation in the prevention of coronary artery restenosis after angioplasty has generated much recent interest. Animal research and pilot clinical efforts have focused primarily on intraluminal methods of radiation delivery. This article reviews the experience to date with external beam radiation in restenosis prevention and suggests issues that should be considered from the standpoint of both external beam and intravascular radiotherapy. External beam radiation can certainly play an effective role in clinical studies of coronary artery restenosis, and a multicenter randomized trial of external beam radiation after coronary angioplasty has been initiated.
Assuntos
Doença das Coronárias/radioterapia , Angioplastia Coronária com Balão , Animais , Braquiterapia , Terapia Combinada , Doença das Coronárias/prevenção & controle , Doença das Coronárias/terapia , Cardiopatias/etiologia , Humanos , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Ratos , RecidivaRESUMO
Although several studies have suggested that inhibition of arterial narrowing by radiation after angioplasty is dependent on both time and dose, little is known regarding the temporal aspects of this effect and the mechanisms by which radiation affects the response of smooth muscle cells to injury. To determine the time course of inhibition of intimal hyperplasia by radiation, 135 rats were given single-fraction external gamma irradiation (1-10 Gy) to one carotid artery at intervals from 5 days before to 5 days after bilateral carotid artery balloon catheter injury, and intimal cross-sectional area was determined from histological sections at 20 days after injury. There was a prominent time- and dose-dependent inhibition of intimal hyperplasia by radiation when it was administered before or after balloon injury, with the greatest effect noted within 24 h before or after injury. To investigate the effect of radiation on smooth muscle cell growth (by cell counting) and proliferation, cell cycle kinetics (by BrdU incorporation), and cell killing (by clonogenic assay), smooth muscle cell cultures derived from rat aortic explants were seeded in equine plasma to induce quiescence, and radiation (2.5-10 Gy) was administered at various intervals before or after synchronous growth stimulation by 10% whole blood serum. A similar time and dose dependence was noted in growth kinetics, BrdU incorporation and cell killing for smooth muscle cells irradiated in vitro; in each case, the effect was most prominent for radiation administered in temporal proximity to stimulation with whole blood serum. By Western blot analysis, cultured smooth muscle cells showed a rapid time-dependent increase in Cdkn1a (formerly known as p21) protein expression, followed by a delayed increase in Tp53 (formerly known as p53) expression after irradiation. Activation of intracellular caspases, manifest by proteolytic poly(ADP-ribose) polymerase (PARP) cleavage, was not detected in smooth muscle cell cultures after irradiation. These observations suggest that radiation limits intimal hyperplasia in vivo by a transient, reversible process. Although apparent cytotoxic injury occurs in vitro, apoptosis of smooth muscle cells is not apparent. Both inhibition of proliferation of smooth muscle cells and cell cycle delay may contribute to inhibition of intimal hyperplasia in vivo by radiation.
Assuntos
Artérias/patologia , Divisão Celular/efeitos da radiação , Músculo Liso/efeitos da radiação , Animais , Artérias/metabolismo , Western Blotting , Caspases/metabolismo , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/metabolismo , Ativação Enzimática , Hidrólise , Hiperplasia , Masculino , Músculo Liso/metabolismo , Músculo Liso/patologia , Poli(ADP-Ribose) Polimerases/metabolismo , Ratos , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/metabolismoRESUMO
Treatment of confluent monolayers of bovine aortic endothelial cells (BAEC) with gamma rays resulted in the delayed appearance of cells with an enlarged surface area that were morphologically similar to senescent cells. The majority of these cells stained positively for senescence-associated beta-galactosidase (SA-beta-gal), indicating that these cells are biochemically similar to senescent cells. The incidence of the senescence-like phenotype increased with dose (5-15 Gy) and time after irradiation. Cells with a senescence-like phenotype began to appear in the monolayer several days after irradiation. The onset of the appearance of this phenotype was accelerated by subculturing 24 h after irradiation. This acceleration was not entirely due to stimulation of progression through the cell cycle, since a high percentage of the senescent-like cells that appeared after subculture were not labeled with BrdUrd during the period after subculture. Prolonged up-regulation of expression of CDKN1A (also known as p21(CIP1/WAF1)) after irradiation was noted by Western blot analysis, again suggesting a similarity to natural senescence. Phenotypically altered endothelial cells were present in the irradiated monolayers as long as 20 weeks after irradiation, suggesting that a subpopulation of altered endothelial cells that might be functionally deficient could persist in the vasculature of irradiated tissue for a prolonged period after irradiation.
Assuntos
Aorta/efeitos da radiação , Senescência Celular/efeitos da radiação , Endotélio Vascular/efeitos da radiação , Animais , Aorta/citologia , Aorta/metabolismo , Bromodesoxiuridina/metabolismo , Bovinos , Células Cultivadas , Inibidor de Quinase Dependente de Ciclina p21 , Ciclinas/genética , Relação Dose-Resposta à Radiação , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Genes cdc , FenótipoRESUMO
To demonstrate the effect of gamma radiation on proliferating smooth muscle cells in vivo, a standardized bilateral carotid balloon catheter arterial injury was produced in 45 rats and doses from 0-20 Gy were delivered to the right carotid artery at 24 h after injury. At 20 days after injury, cross-sectional area of intima was determined from axial histological sections. Compared to contralateral, nonirradiated balloon-injured arteries, radiation produced a significant dose-dependent reduction in intimal cross-sectional area, with a 50% decrease at 5-7.5 Gy. To determine the effect of timing of irradiation on intimal hyperplasia, 30 rats with bilateral carotid injury received unilateral cervical irradiation at doses of 1, 5 or 10 Gy administered at either 1, 3 or 5 days after injury. The radiation dose (P = 0.0002), timing of irradiation (P = 0.003) and an interaction between timing and dose (P = 0.0278) were significantly associated with reduction in neointimal cross-sectional area. To determine the effects of radiation on intimal hyperplasia at later intervals, rats irradiated with 15 (n = 5) or 20 Gy (n = 5) were euthanized at 3 months after injury. A significant persistent reduction in intimal cross-sectional area for irradiated arteries at 3 months was associated with minimal apparent radiation effects upon adjacent tissue. These data suggest that external gamma irradiation at the single doses used effectively inhibits smooth muscle proliferation and intimal hyperplasia in the rat balloon catheter injury model in a time- and dose-dependent manner.
Assuntos
Músculo Liso Vascular/efeitos da radiação , Angioplastia com Balão/efeitos adversos , Animais , Artérias Carótidas/patologia , Artérias Carótidas/efeitos da radiação , Movimento Celular , Relação Dose-Resposta à Radiação , Hiperplasia , Masculino , Músculo Liso Vascular/patologia , Lesões Experimentais por Radiação/etiologia , Ratos , Ratos Sprague-DawleyRESUMO
Two brain-specific proteins, S-100beta and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100beta levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100beta is a marker of blood-brain barrier (BBB) leakage rather than of neuronal damage. We measured both proteins in the plasma of patients undergoing iatrogenic BBB disruption with mannitol, followed by chemotherapy. Serum S-100beta increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100beta is an early marker of BBB opening that is not necessarily related to neuronal damage.
Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Neoplasias do Sistema Nervoso Central/sangue , Linfoma/sangue , Manitol/administração & dosagem , Proteínas S100/sangue , Biomarcadores/sangue , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Esquema de Medicação , Humanos , Infusões Intra-Arteriais , Linfoma/tratamento farmacológico , Fatores de Crescimento Neural , Fosfopiruvato Hidratase/sangue , Valor Preditivo dos Testes , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
How the brain meets its continuous high metabolic demand in light of varying plasma glucose levels and a functional blood-brain barrier (BBB) is poorly understood. GLUT-1, found in high density at the BBB appears to maintain the continuous shuttling of glucose across the blood-brain barrier irrespective of the plasma concentration. We examined the process of glucose transport across a quasi-physiological in vitro blood-brain barrier model. Radiolabeled tracer permeability studies revealed a concentration ratio of abluminal to luminal glucose in this blood-brain barrier model of approximately 0.85. Under conditions where [glucose](lumen) was higher than [glucose](ablumen), influx of radiolabeled 2-deoxyglucose from lumen to the abluminal compartment was approximately 35% higher than efflux from the abluminal side to the lumen. However, when compartmental [glucose] were maintained equal, a reversal of this trend was seen (approximately 19% higher efflux towards the lumen), favoring establishment of a luminal to abluminal concentration gradient. Immunocytochemical experiments revealed that in addition to segregation of GLUT-1 (luminal>abluminal), the intracellular enzyme hexokinase was also asymmetrically distributed (abluminal>luminal). We conclude that glucose transport at the CNS/blood interface appears to be dependent on and regulated by a serial chain of membrane-bound and intracellular transporters and enzymes.
Assuntos
Barreira Hematoencefálica/fisiologia , Glucose/metabolismo , Proteínas de Transporte de Monossacarídeos/metabolismo , Animais , Astrócitos/citologia , Astrócitos/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Radioisótopos de Carbono/farmacocinética , Bovinos , Compartimento Celular/efeitos dos fármacos , Compartimento Celular/fisiologia , Diferenciação Celular/fisiologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/fisiologia , Células Cultivadas , Técnicas de Cocultura , Desoxiglucose/farmacocinética , Endotélio Vascular/citologia , Endotélio Vascular/metabolismo , Feto , Transportador de Glucose Tipo 1 , Hexoquinase/metabolismo , Imuno-Histoquímica , Membranas Artificiais , Proteínas de Transporte de Monossacarídeos/efeitos dos fármacos , Fenótipo , RatosRESUMO
A comparison was made of different treatment plans to determine the effect on the three-dimensional dose distributions of varying the allowed parameters in linac-based stereotactic radiosurgery with circular collimators; these parameters are arc position, length, and weighting, and collimator diameter. For the class of eccentrically shaped target volumes that are not so irregular as to require several separate isocenters, it was found that superior dose distributions could be achieved by varying arc length, arc position, arc weighting, and collimator diameter. An analysis of the results achieved with an automated planning program indicates that, in general, the variables of arc position and arc length are of greater importance than collimator size or beam weighting. However, there are cases where varying these latter two parameters does result in markedly better dose distributions. A deeper investigation into the effects of multiple collimators on the dose distribution in the area of steepest gradient demonstrated that multiple collimator sizes do not significantly degrade the dose falloff, which is in fact mostly determined by the effects of intersecting arcs.
Assuntos
Neoplasias Encefálicas/cirurgia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador , Radioterapia Assistida por Computador , Neoplasias Encefálicas/secundário , Humanos , Estudos RetrospectivosRESUMO
To determine the optimal postoperative interval after which heparin therapy can be safely initiated, a rat model for experimental craniotomy and corticectomy was developed. In 50 rats (100 lesions), heparin therapy was initiated 1, 2, 3, 5, or 7 days after standardized bilateral frontal corticectomy and was continued for 7 days. Intraperitoneally administered heparin, 75 to 100 U/kg.h, was continuously given to maintain the activated partial thromboplastin time in one of two ranges: therapeutic (1.5-3 times control) or supratherapeutic (> 3 times control). The size of intracranial hemorrhage was determined from coronal brain sections by automated image analysis. No significant hemorrhage was observed in control (saline infusion) animals or in rats receiving therapeutic doses of heparin beginning more than 24 hours after surgery. Small (10-50 mm3) and large (> 50 mm3) hemorrhages were frequent at all intervals up to 5 days in animals with supratherapeutic activated partial thromboplastin time (P < 0.01). Judicious heparin therapy may be safely initiated at 48 hours after craniotomy and corticectomy in rats, whereas supratherapeutic anticoagulation is associated with intracranial hemorrhage at intervals of up to 5 days.
Assuntos
Córtex Cerebral/cirurgia , Heparina/efeitos adversos , Animais , Encéfalo/patologia , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/patologia , Relação Dose-Resposta a Droga , Hematoma/induzido quimicamente , Hematoma/patologia , Heparina/administração & dosagem , Masculino , Cuidados Pós-Operatórios , Ratos , Ratos Sprague-Dawley , Fatores de RiscoRESUMO
The local effect of the calcium channel antagonist diltiazem and the protein kinase inhibitor 1-5-(isoquinoline sulfonyl)-5-homopiperazine HCL (HA1077) on neointimal formation after arterial injury were investigated by the use of a perivascular drug-delivery system. Bilateral carotid artery balloon injury was produced in 130 rats. In six groups of 10 rats each, diltiazem or HA1077 at three doses (low, 0.2 mg; medium, 1 mg; high, 5 mg) was mixed with the drug-delivery polymer poly(vinyl) alcohol and applied to the adventitial surface of the injured right carotid artery enclosed by a Silastic cuff; 10 control animals received polyvinyl alcohol only in the silastic cuff. In all animals, the contralateral injured artery without the cuff served as a control. At 10 and 20 days after the injury, the intimal cross-sectional area was determined from light microscopic sections for the injured segment of both carotid arteries. In six additional groups of 10 rats each, treated as above, levels of diltiazem and HA1077 in plasma were measured at periods from 1 hour to 5 days after perivascular application. At 10 days after endothelial injury, animals receiving high-dose diltiazem or HA 1077 (5 mg) demonstrated significant reductions in neointimal area compared with polyvinyl alcohol controls for both treated and contralateral untreated vessels. At 20 days after injury, neointimal hyperplasia was inhibited only on the treated side in both high-dose groups. Perivascular diltiazem and HA1077 at lower doses (1 or 0.2 mg) did not affect neointimal area at 10 or 20 days in either treated or untreated arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Artérias/lesões , Cateterismo/instrumentação , Diltiazem/farmacologia , Displasia Fibromuscular/patologia , Túnica Íntima/efeitos dos fármacos , Administração Tópica , Animais , Artérias/patologia , Artérias Carótidas/patologia , Lesões das Artérias Carótidas , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Ratos , Ratos Sprague-Dawley , Túnica Íntima/patologiaRESUMO
Segmental endothelial desquamation of the common carotid artery was produced in 30 rats using a balloon catheter technique which produces consistent proliferation of intimal smooth muscle cells from 5 to 20 days after injury. Immediately after endothelial injury, 15 animals were treated with periadventitial application of heparin contained in a continuous-release drug-delivery system using the polymer polyvinyl alcohol (PVA) and PVA alone applied in a similar fashion to 15 control rats. Animals were killed at 5, 10 and 20 days, respectively, after surgery by intracardiac perfusion-fixation, and vessels were prepared for light microscopy, scanning electron microscopy, and immunohistochemistry with antibodies directed against actin. At all time periods, there was a significant reduction in intimal cross-sectional area in heparin/PVA-treated vessels compared to control vessels. Scanning electron microscopy showed complete absence of endothelial cells from the luminal surface in both control and treated arteries at all time periods without evidence of significant platelet aggregation. Immunohistochemistry demonstrated the presence of immunoreactive actin in the proliferating myointimal cells. Femoral venous prothrombin time and partial thromboplastin time were unchanged in heparin/PVA-treated animals compared to controls at 1, 5, and 10 days. Continuous-release polymer drug delivery can be used to apply heparin selectively to the adventitial surface of vessels and effect changes in the vessel wall over periods of up to 3 weeks. By this means, smooth muscle proliferation and subsequent vessel narrowing after endothelial injury were inhibited without systemic anticoagulation. This technique may be applicable to both clinical and research applications related to the pathophysiology of arterial injury.
Assuntos
Doenças das Artérias Carótidas/tratamento farmacológico , Heparina/administração & dosagem , Músculo Liso Vascular/patologia , Animais , Testes de Coagulação Sanguínea , Doenças das Artérias Carótidas/patologia , Preparações de Ação Retardada , Implantes de Medicamento , Masculino , Microscopia Eletrônica de Varredura , Músculo Liso Vascular/efeitos dos fármacos , Ratos , Ratos EndogâmicosRESUMO
OBJECTIVE AND IMPORTANCE: The development of a venous aneurysm associated with dural arteriovenous malformations rarely has been documented in the literature. CLINICAL PRESENTATION: A 64-year-old man with known dural arteriovenous malformations developed a venous aneurysms, as shown on sequential angiograms obtained during 2 years. INTERVENTION: The dural arteriovenous malformations were treated with neuroendovascular embolization and then surgical excision. CONCLUSION: The clinical presentation, diagnosis, and treatment of this unusual case are presented.
Assuntos
Angiografia Digital , Angiografia Cerebral , Dura-Máter/irrigação sanguínea , Aneurisma Intracraniano/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Veias Cerebrais/diagnóstico por imagem , Veias Cerebrais/cirurgia , Terapia Combinada , Embolização Terapêutica , Humanos , Aneurisma Intracraniano/cirurgia , Malformações Arteriovenosas Intracranianas/cirurgia , Masculino , Pessoa de Meia-IdadeRESUMO
Radiation therapy plays a critical role in the treatment of central nervous system neoplasms and cerebral arteriovenous malformations. The deleterious effects of radiation on cerebral arteries may be the primary limitation to these treatment methods, as radiation may cause a variety of cerebrovascular injuries and hemodynamic changes. Radiation-induced changes in the cerebral arterial wall are determined by a number of cellular processes in endothelium and smooth muscle cells that modulate differences in radiosensitivity and phenotypic expression. The histopathological findings in arterial radiation injury include vessel wall thickening, thrombosis, luminal occlusion, and occasional telangiectases. Mechanisms for radiation injury to blood vessels include phenotypic changes in normal vessel wall cells (especially endothelium) manifested by the expression or suppression of specific gene and protein products that affect cell cycle progression or cellular proliferation or demise via cytotoxic injury or apoptosis. This review describes the molecular and cellular events involved in the systemic and cerebral vascular response to radiation and the potential means by which these responses may be influenced to augment the therapeutic effects of radiation while minimizing the untoward consequences.
Assuntos
Artérias Cerebrais/efeitos da radiação , Animais , Capilares/efeitos da radiação , Dano ao DNA , Endotélio Vascular/efeitos da radiação , Expressão Gênica/efeitos da radiação , HumanosRESUMO
Factor XIII is an endogenous clotting factor that retards thrombus degradation by cross-linking fibrin. To determine the efficacy of Factor XIII as a topical clot-stabilizing agent in preventing postoperative hemorrhage associated with coagulopathy, a rat model of experimental craniotomy and standardized bilateral frontal corticectomy was developed. In 25 rats (50 lesions), recombinant human Factor XIII or placebo solution was topically applied to corticectomy cavities after hemostasis was achieved; each animal served as its own control. In 20 rats, heparin sulfate (100 U/kg.h) was initiated intraperitoneally 3 days after surgery and was continually administered by an Alzet pump for 7 days, compared with a control group of 5 rats receiving saline intraperitoneally. The volume of intracranial hemorrhage was quantitatively determined from coronal sections by use of automated image analysis. Large (> 50 mm3) intracerebral hemorrhages were significantly more frequent in placebo (60%)- compared with recombinant Factor XIII (15%)-treated lesions (P < 0.01) in animals receiving heparin. The topical application of clot-stabilizing agents such as Factor XIII may reduce the risk of postoperative intracranial hemorrhage, especially in high-risk patients with coagulopathy.
Assuntos
Hemorragia Cerebral/prevenção & controle , Fator XIII/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Administração Tópica , Animais , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/patologia , Fator XIII/uso terapêutico , Lobo Frontal/cirurgia , Hematoma/etiologia , Hematoma/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Proteínas RecombinantesRESUMO
A new animal model for vasospasm using rat femoral artery has been developed. Whole blood, washed erythrocytes, or leukocytes in platelet-rich plasma were selectively applied to the adventitial surface of the femoral artery for 7 days in 15 rats, after which the vessels were perfusion-fixed and examined by light and transmission electron microscopy and immunohistochemistry. As compared with matched control arteries, there was a prominent reduction in luminal cross-sectional area after 7 days in vessels exposed to whole blood or washed erythrocytes, but not in those exposed to leukocytes in platelet-rich plasma. In arteries with luminal narrowing, light and transmission electron microscopy demonstrated marked morphological changes throughout the vessel wall similar to those seen in cerebral vasospasm after subarachnoid hemorrhage. Immunohistochemistry disclosed a prominent loss of immunoreactive actin in smooth muscle cells of arteries exposed to whole blood or erythrocytes. To assess the time course of arterial narrowing in this model, whole blood was selectively applied to the adventitial surface of femoral arteries in 23 rats for periods from 2 to 20 days. As compared with control arteries, arterial narrowing was variably present at 2 days, progressively increased by 5 days, was maximal at 7 to 10 days, and returned to near control levels by 20 days. The presence and severity of ultrastructural changes in vessel wall corresponded to the degree of arterial narrowing over time. These results suggest that chronic narrowing in rat femoral artery exposed to periadventitial blood is analogous to that observed in cerebral arterial vasospasm after subarachnoid hemorrhage. This new model represents a simple and reliable means to investigate pathogenic mechanisms and potential therapies for vasospasm.