RESUMO
BACKGROUND: During endoscopic neurosurgery, direct mechanical stimulation of the brain by the endoscope and increased intracranial pressure (ICP) caused by the continuous rinsing can induce potentially lethal haemodynamic reflexes, brain ischaemia, and excessive fluid resorption. METHODS: In a newly presented rat model of endoscopic neurosurgery, stereotactic access to the cerebrospinal fluid was secured and the ICP was increased by controlled infusion until complete suppression of the cerebral perfusion pressure (CPP). The haematocrit (Hct) level was determined before and after the procedure. During the whole procedure, invasive arterial pressure, ICP, and heart rate were continuously recorded and evaluated in a subsequent offline analysis. After the procedure, the animals were allowed to recover and 7 days later they were killed for histological examination. RESULTS: Suppression of the CPP resulted in a severe hypertension combined with tachycardia or mild bradycardia. The Hct decreased from 41 to 35 over the minutes of CPP suppression. After cessation of the infusion, the ICP decreased to 37% of the plateau pressure within 2.5 s. In the first few minutes after restoration of normal ICP, five animals died because of pulmonary oedema. CONCLUSIONS: Upon complete suppression of the CPP, an obvious hypertension developed, often together with tachycardia, but no severe bradycardia. At high ICP levels, we observed an important translocation of irrigation fluid to the vascular space. Fatality was not caused by ischaemia or arrhythmia but due to pulmonary oedema.
Assuntos
Circulação Cerebrovascular , Hipertensão Intracraniana/fisiopatologia , Neuroendoscopia/efeitos adversos , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Frequência Cardíaca , Hematócrito , Hipertensão Intracraniana/diagnóstico , Hipertensão Intracraniana/etiologia , Pressão Intracraniana , Masculino , Monitorização Intraoperatória/métodos , Edema Pulmonar/etiologia , Ratos , Ratos Wistar , Taquicardia/etiologia , Irrigação Terapêutica/efeitos adversosRESUMO
Acute obstruction of the middle cerebral artery (MCA) was obtained by injecting a single autologous blood clot into the internal carotid artery of dogs. The technique induced very reproducible unilateral ischemic lesions in the MCA territory; hemorrhagic transformation of the lesions was often seen. The hemodynamic and metabolic effects of blood clot embolism were studied in 35 dogs with positron emission tomography (PET) and the 15O steady-state technique, and compared with a control group of seven intact animals. In the acute phase, the involved brain tissue still had a nearly normal oxygen consumption (-11%) despite the lowered tissue perfusion (-20%) caused by the vascular obstruction. The lowered oxygen availability was compensated by an increased oxygen extraction ratio (+11%). Twenty-four hours after the insult, the hemodynamic situation had barely changed, and the ischemic event had evolved into a brain infarct in which oxygen consumption was clearly lowered (-25%) and accompanied by a significant lowering (-22%) of the oxygen extraction ratio compared with the acute situation. Therapeutic thrombolysis by local administration of streptokinase (500,000 IU), starting 30 min after the insult, was not able to salvage any brain tissue or to ameliorate tissue perfusion despite angiographically confirmed clot lysis. However, when fibrinolytic therapy was started within the first 5 min after the insult, hemispheric blood flow was normalized, and most of the threatened brain tissue was salvaged, as was indicated by its normalized oxygen consumption and oxygen extraction ratio. Early fibrinolysis was accompanied by definite clinical improvement and substantial reduction in the severity of the morphological lesions that were never hemorrhagic.
Assuntos
Circulação Cerebrovascular , Transtornos Cerebrovasculares/diagnóstico por imagem , Fibrinolíticos/uso terapêutico , Embolia e Trombose Intracraniana/complicações , Estreptoquinase/uso terapêutico , Tomografia Computadorizada de Emissão , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Angiografia Cerebral , Transtornos Cerebrovasculares/tratamento farmacológico , Transtornos Cerebrovasculares/etiologia , Consumo de OxigênioRESUMO
The effect of flunarizine and methylprednisolone on the recovery of somatosensory evoked potentials (SEPs) was evaluated in an experimental model of spinal cord impact injury in anesthetized cats. In addition, the effect of flunarizine on posttraumatic spinal cord blood flow (SCBF) (using the hydrogen clearance technique) and interstitial calcium and potassium activity (ion-selective electrodes) was investigated. After the injury (600 g.cm), SEPs disappeared, followed by a spontaneous recovery to 17% of the preinjury amplitude at the end of the 4 h observation period. Flunarizine treatment (0.1 mg/kg IV, given 5 and 120 min after injury) resulted in a significantly improved recovery of SEPs, reaching 52% of the preinjury amplitude. Methylprednisolone treatment (30 mg/kg IV, given 5 min after injury) resulted in a 30% recovery level, significantly better than in untreated animals but significantly inferior to flunarizine treatment. Combination of both treatments resulted in a 62% recovery level, significantly better than after methylprednisolone treatment alone. Flunarizine treatment had no significant effect on the postinjury evolution of SCBF and interstitial potassium activity; it did, however, significantly accelerate the recovery of interstitial calcium activity, which sharply decreased immediately after injury. It is concluded that intravenous administration of the calcium entry blocker flunarizine improves the functional recovery of the spinal cord in the acute phase after experimental spinal impact injury. The observed improvement is not achieved by an effect on local blood flow but is possibly related to an inhibitory effect of the drug on cellular calcium entry.
Assuntos
Flunarizina/uso terapêutico , Metilprednisolona/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Cálcio/metabolismo , Gatos , Potenciais Somatossensoriais Evocados/efeitos dos fármacos , Potenciais Somatossensoriais Evocados/fisiologia , Feminino , Masculino , Potássio/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Medula Espinal/irrigação sanguínea , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologiaRESUMO
The effect of the calcium entry blocker flunarizine on a high-potassium induced increase of intracellular free calcium was studied. The experiments were done with neurons isolated from rat dorsal root ganglia and loaded with the calcium-sensitive dye fura-2. The increase of calcium induced by 60 mmol/l potassium was abolished after removal of extracellular calcium, was reversibly reduced by 50 mumol/l cadmium (76% inhibition), 50 mumol/l nickel (25% inhibition) and 10 mumol/l nifedipine (18% inhibition), and reversibly increased after removal of extracellular sodium (26% increase). The potassium induced increase of intracellular calcium is, therefore, mediated by transmembrane calcium influx, probably to a large extent through cadmium-sensitive calcium channels. Flunarizine (5 min incubation followed 1 min wash-out) reduced the amplitude of the high-potassium induced calcium increase in a dose-dependent manner (Kd = 370 +/- 100 nmol/l; mean +/- SEM; n = 8), causing complete inhibition at a concentration of 10 mumol/l in the majority of cells. Flunarizine (> or = 1 mumol/l) caused a reversible increase of the resting level of intracellular calcium in some cells, an effect which disappeared in the absence of extracellular calcium. The drug (1 mumol/l had no influence on the time course of recovery of intracellular calcium subsequent to a rise induced by high-potassium or by the calcium ionophore A23,187. It is concluded that flunarizine acts as an inhibitor of depolarization-mediated calcium influx. At a concentration of 1 mumol/l, the drug presumably has no effect on cellular calcium extrusion and/or sequestration mechanisms.
Assuntos
Canais de Cálcio/efeitos dos fármacos , Flunarizina/farmacologia , Gânglios Espinais/metabolismo , Neurônios/metabolismo , Animais , Cálcio/metabolismo , Cálcio/farmacologia , Cálcio/fisiologia , Bloqueadores dos Canais de Cálcio/farmacologia , Fura-2 , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Técnicas In Vitro , Neurônios/efeitos dos fármacos , Potássio/farmacologia , Ratos , Ratos Wistar , Sódio/fisiologiaRESUMO
4-[123I]Iodo-N-[2-[4-(6-trifluoromethyl-2-pyridinyl)-1-piperazinyl]ethyl]benzamide (1.123I), a potential SPECT 5-HT(1A) radioligand, was evaluated in vivo in rats. Biodistribution studies were performed leading to a % ID in the brain of 0.22 at 5 min p.i. No significant differences in % ID/g tissue of the different isolated brain regions (hippocampus, hypothalamus, striatum, cortex and cerebellum) could be demonstrated. Blocking experiments with 8-OH-DPAT, WAY100635 and ketanserin could not show any significant change in tracer uptake in the isolated brain regions. These data suggest that uptake in the brain does not represent binding of 1.123I to the 5-HT(1A) receptor.
Assuntos
Benzamidas/farmacocinética , Encéfalo/metabolismo , Piperazinas/farmacocinética , Receptores de Serotonina/metabolismo , Antagonistas da Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Tomografia Computadorizada de Emissão de Fóton Único , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Benzamidas/síntese química , Encéfalo/diagnóstico por imagem , Ketanserina/farmacologia , Masculino , Piperazinas/síntese química , Piperazinas/farmacologia , Piridinas/farmacologia , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Receptores de Serotonina/efeitos dos fármacos , Receptores 5-HT1 de Serotonina , Distribuição TecidualRESUMO
Adaptation of the circulation to pregnancy occurs via a complicated series of changes not yet completely understood. To define pertinent alterations, echocardiographic measurements of left ventricular function were performed every 4 weeks in 13 normal pregnant women. Six weeks postpartum each women was reexamined; thus each woman served as her own nonpregnant control. Left ventricular dimensions, left venticular wall thickness, shortening fraction, and rate of change of these measurements were recorded. As expected, cardiac output was increased throughout pregnancy. Up to 20 weeks gestation this occurred via an increased heart rate. After 20 weeks gestation stroke volume increased significantly, with 20% at 20--26 weeks up to 30% at term (p < 0.01). With the end-diastolic wall thickness remaining equal, myocardial hypertrophy occurred. This was corroborated by an increase in end-systolic left ventricular wall thickness towards term: from 13.8 mm (S.D. +/- 1.73) in early pregnancy to 16.6 mm (S.D. +/- 1.62) at term, with end-systolic left ventricular dimension unchanged. It was concluded that during pregnancy the mechanism to produce a higher cardiac output shifts from an increase in cardiac frequency to elevation of stroke volume with concomitant myocardial hypertrophy. Due to changes in heart rate and afterload, no conclusions could be drawn regarding myocardial contractility.
Assuntos
Adaptação Fisiológica , Coração/fisiologia , Gravidez , Adulto , Ecocardiografia , Feminino , Frequência Cardíaca , Humanos , Contração Miocárdica , Período Pós-Parto , Volume Sistólico , Função VentricularRESUMO
In order to gain more insight into the pathophysiology of extracerebral cerebrovascular occlusion, the cerebral hemodynamic behaviour after uni- or bilateral carotid occlusion was investigated. In Wistar rats, acute occlusion of one common carotid artery leads to a moderate bilateral lowering of the resting hemispheric brain blood flow; no interhemispheric perfusion asymmetry is observed. During hypercapnia, however, a manyfold increase of the hemispheric blood flow is seen at the intact side, whereas blood flow increase at the side of the occlusion is suppressed indicating that the cerebrovascular reserve at the side of the occlusion is largely used to preserve resting hemispheric perfusion. During the days (1, 5, 15 and 30) following the occlusion, resting hemispheric blood flow is progressively restored rather rapidly (bilateral normalization on the fifth day) whereas restoration of the cerebrovascular reserve (hemispheric blood flow increase in hypercapnia) proceeds more slowly and a nearly normal hypercapnic response is reached on day thirty. Spontaneously Hypertensive Rats (SHR) show structural abnormalities of their blood vessels during the development of hypertension, leading to impaired adaptation possibilities of the cerebral vasculature after unilateral common carotid occlusion. This is indicated by the striking comparability of the compensation of hemispheric cerebral blood flow (in normo- and hypercapnia) of SH rats five days after unilateral carotid occlusion with the cerebral hemodynamic status of normotensive animals already seen 24 hours after the same occlusion. Consecutive bilateral common carotid occlusion shows that survival rate increases by increasing the interval between both occlusions. This survival relation is much more unfavorable in SH rats. The parallelism between the restoration of the measured CO2-reactivity of the blood flow in the involved hemisphere after unilateral carotid occlusion and the evolution of survival rate after consecutive bilateral carotid occlusion indicates that the response of the hemispheric circulation to CO2 offers a good estimate of true cerebrovascular reserve after cerebrovascular accidents of this kind. In cats, acute bilateral occlusion of the carotid arteries leads to a moderate decrease of resting cerebral blood flow in the anterior parts of the brain (cerebrum); the hypercapnic response of this region is, however, completely abolished. In the posterior brain regions (medulla oblongata and cerebellum) resting blood flow and its increase under hypercapnia are preserved. The experiments indicate that the relative preservation of resting cerebral blood flow in the cerebrum of the cat after acute bilateral carotid occlusion is at the expense of its complete hemodynamic reserve. Posterior brain regions are better protected in these conditions.(ABSTRACT TRUNCATED AT 400 WORDS)
Assuntos
Adaptação Fisiológica , Arteriopatias Oclusivas/fisiopatologia , Doenças das Artérias Carótidas/fisiopatologia , Circulação Cerebrovascular , Animais , Dióxido de Carbono/sangue , Gatos , Masculino , Ratos , Ratos Endogâmicos SHR , Ratos EndogâmicosRESUMO
The introduction of positron emission tomography (PET) to study the cerebral circulation and metabolism is for the present the last step in the evolution of a technology which started 40 years ago with the gas clearance method developed by Kety and Schmidt. To study cerebral blood flow and metabolism in humans the steady state 15O method (Frackowiak et al., 1980) is widely used in different PET centers. We have used this method in experimental animals. The principles of the method and the mathematical models which are at the basis of the calculation of cerebral blood flow (CBF) and oxygen metabolism (cerebral metabolic rate for oxygen, CMRO2 and oxygen extraction ratio, OER) are relatively simple but during its application in vivo several problems arise as described. The steady state method of Frackowiak et al. allowed in our experiments the accurate measurement of cerebral blood flow and oxygen metabolism in anesthetized dogs. We have investigated the effect of experimental cerebral embolism in different series of experiments. Two different models of cerebral ischemia were assessed. In the first model focal ischemia was produced by infusing Sephadex particles (mean diameter 40 microns) into the left common carotid artery; in the second model an autologous blood clot (100 microliters) was injected into the left internal carotid artery. With both procedures the ischemia was practically limited to the ipsilateral hemisphere. Moreover in the two models the effects of ischemia were very reproducible. This is probably due to the good standardization of the embolization procedures. The results clearly indicate a differential effect of microembolization with particles and blood clot embolization, illustrating the importance of the technique used to produce cerebral embolization in experimental animals. PET offers possibilities for diagnosis of cerebral ischemia. At variance with the classical techniques for studying cerebral blood flow PET also allows simultaneous assessment of cerebral metabolism and to differentiate between brain tissue which is irreversible damaged and tissue which can be potentially salvaged. Therefore PET also offers new possibilities in clinical and experimental research. The reproducible effects obtained with the blood clot model, the metabolic cerebral effects of which are similar to those of clinical stroke, will allow to study the effect of different therapeutic approaches for stroke such as thrombolysis and calcium entry blockade.
Assuntos
Encéfalo/metabolismo , Circulação Cerebrovascular , Tomografia Computadorizada de Emissão , Animais , Cães , Embolia e Trombose Intracraniana/fisiopatologia , Consumo de Oxigênio , Radioisótopos de OxigênioRESUMO
A dorsal laminectomy of L-4, L-5, and L-6, followed by resection of the dorsal (afferent) roots of the gastrocnemius muscle (desafferentation) was performed on 3 calves which had spastic paralysis. All signs of the condition disappeared after desafferentation. This suggests an overactive stretch reflex to be the cause of the spastic paralysis.
Assuntos
Doenças dos Bovinos/cirurgia , Espasticidade Muscular/veterinária , Músculos/inervação , Raízes Nervosas Espinhais/cirurgia , Vias Aferentes/cirurgia , Animais , Bovinos , Feminino , Espasticidade Muscular/cirurgiaRESUMO
Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations were determined in the cerebrospinal fluid (CSF) of 28 normal calves and 29 spastic calves. Concentrations of HVA were significantly (P less than 0.01) lower in spastic calves, whereas differences in 5-HIAA concentrations were not found between normal and spastic calves. These findings indicate that a lower dopaminergic metabolism takes place in the central nervous system (CNS) of spastic calves.
Assuntos
Doenças dos Bovinos/líquido cefalorraquidiano , Ácido Homovanílico/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Espasticidade Muscular/veterinária , Fenilacetatos/líquido cefalorraquidiano , Animais , Bovinos , Espasticidade Muscular/líquido cefalorraquidianoAssuntos
Artrite Infecciosa/veterinária , Doenças dos Bovinos/terapia , Animais , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Artrite Infecciosa/diagnóstico por imagem , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/cirurgia , Artrite Infecciosa/terapia , Ossos do Carpo , Moldes Cirúrgicos , Bovinos , Doenças dos Bovinos/diagnóstico por imagem , Doenças dos Bovinos/tratamento farmacológico , Doenças dos Bovinos/cirurgia , Desbridamento , Feminino , Membro Anterior , Membro Posterior , Injeções Intra-Articulares , Masculino , Fenilbutazona/administração & dosagem , Fenilbutazona/uso terapêutico , Radiografia , Suturas , Ossos do TarsoRESUMO
Interstitial and tissue cations and electrical potential were studied in an experimental model of spinal cord contusion injury in anaesthetised cats. Measurements of interstitial ion activity in the grey matter at the injury site (with ion-selective electrodes), showed a decrease of sodium and calcium, an increase of potassium, a small acidification and a negative shift in the electrical potential 5 min after injury. The interstitial ionic changes were completely reversible within 90 min following injury. Measurements of the ion content in a tissue sample from the injury site (flame photometry) showed an increase of sodium and calcium and a decrease of potassium 5 min after injury. The magnitude of the post-injury sodium change was much larger than the potassium change, both for interstitial and tissue measurements. Treatment of the animals with the calcium entry blocker flunarizine before the injury did not influence the magnitude of post-injury interstitial calcium decrease but significantly increased the rate of subsequent recovery. Pre-injury flunarizine treatment also significantly increased the recovery rate of the electrical potential. The experiments suggest the occurrence of a net ionic shift towards the intracellular space, which may contribute to oedema formation in the very early post-injury period. The post-injury decrease of interstitial calcium activity is probably not mediated by flunarizine-sensitive calcium entry mechanisms; such mechanisms may, however, be involved in the subsequent recovery period for interstitial calcium activity. Calcium ions may be involved in the recovery process of the negative electrical potential after injury.
Assuntos
Cátions/metabolismo , Contusões/fisiopatologia , Espaço Extracelular/fisiologia , Traumatismos da Medula Espinal/fisiopatologia , Medula Espinal/fisiopatologia , Animais , Cálcio/metabolismo , Cátions/sangue , Gatos , Eletrofisiologia , Feminino , Flunarizina/farmacologia , Masculino , Fatores de TempoRESUMO
Cerebral blood flow in the cat was studied before and after acute bilateral common carotid occlusion under normocapnic and hypercapnic conditions and after induced hypotension. Regional blood flow to different brain structures was studied with the microsphere method. Local blood flow in the caudate nucleus, the cerebral cortex and medulla oblongata was studied with H2-polarography. Although the blood flow to the anterior brain regions is significantly decreased after bilateral common carotid occlusion, their blood supply is kept above ischaemic levels by re-distribution of the vertebrobasilar flow. Cerebrovascular reserve in anterior brain regions, however, is lost as indicated by the severe impairment of both the flow response to hypercapnia and to blood pressure decrease. After bilateral common carotid occlusion paradoxical CO2-reactions, indicating intracerebral steal, were seen in the caudate nucleus. In posterior brain regions resting blood flow, flow-reaction to hypercapnia and to hypotension are better preserved under these conditions. Measurement of the CBF responses to induced hypercapnia is a dependable test for appreciation of cerebrovascular reserve after cerebrovascular occlusion but may be potentially hazardous where local flow is close to ischaemic levels.
Assuntos
Doenças das Artérias Carótidas/fisiopatologia , Circulação Cerebrovascular , Adaptação Fisiológica , Animais , Gatos , Modelos Animais de Doenças , HemodinâmicaRESUMO
Acute occlusion of one common carotid artery in the anesthetized normocapnic rat results in a moderate cerebral blood flow (CBF) decrease in both cerebral hemispheres. No asymmetrical perfusion is observed when the overall flow in each hemisphere is considered. The increase in blood flow which normally occurs in hypercapnia is strongly impaired in the cerebral hemisphere on the occluded side resulting in an important asymmetrical hemispheric perfusion. The days (1, 5, 15, 30) following unilateral carotid occlusion normal control CBF values are found in both hemispheres in normocapnic conditions. Hemispheric perfusion asymmetry in hypercapnia also becomes progressively less pronounced with time but a slight asymmetry still persists one month after unilateral carotid occlusion.
Assuntos
Arteriopatias Oclusivas/fisiopatologia , Doenças das Artérias Carótidas/fisiopatologia , Circulação Cerebrovascular , Animais , Velocidade do Fluxo Sanguíneo , Hipercapnia/fisiopatologia , Masculino , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
The effect of perfusion of the cerebral ventricles with artificial cerebrospinal fluid containing carbachol on the blood flow in the caudate nucleus of the cat and the possibility to inhibit this effect by anticholinergic drugs was studied by means of the hydrogen clearance technique. After a control period during which both lateral ventricles were perfused with artificial CSF of identical composition, the drug under study was added on one side (experimental side) while the other side continued to be perfused with the control artificial CSF (control side). The blood flow on the experimental side and on the control side were compared. A dose dependent response to carbachol was observed. Lower concentrations of carbachol (10(-6) up to 10(-4)M) caused vasodilatation whereas high concentrations (10(-3)M) caused local vasoconstriction. The increase in the local blood flow caused by the low carbachol concentrations was reduced by both atropine (10(-5)M) and hexamethonium (10(-3)M). The fall in CBF observed with the high carbachol concentration was prevented by atropine (10(-5)M). It may be concluded that low, physiologically more meaningful, carbachol concentrations cause a local vasodilatation due to interaction with both muscarinic and nicotinic receptors.
Assuntos
Carbacol/farmacologia , Núcleo Caudado/irrigação sanguínea , Circulação Cerebrovascular/efeitos dos fármacos , Animais , Atropina/farmacologia , Carbacol/antagonistas & inibidores , Gatos , Núcleo Caudado/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Hexametônio , Compostos de Hexametônio/farmacologia , Injeções Intraventriculares , MasculinoRESUMO
The effect of intraventricular histamine on blood flow in the caudate nucleus of the cat was studied by means of the hydrogen clearance technique. Bilateral ventriculo-cisternal perfusion was installed. After a control period during which both lateral ventricles were perfused with mock CSF with the same composition, the drug under study was added to one side (experimental side) while the other side was perfused further with the control mock SCF (control side). At each point in time, blood flow at the experimental side was compared to that at the control side. Histamine (10(-3) M) caused a severe vasodilatation and this effect was completely antagonised by the H2-receptor blocker cimetidine (10(-2) M). Cimetidine had no vasoactive effects of itself in the concentration used. The H2-receptor agonist Dimaprit (10(-3) M) had a vasodilator effect although less important than histamine. Indirect evidence was gained that H1-receptors are not active in the vascular bed under study.
Assuntos
Núcleo Caudado/irrigação sanguínea , Circulação Cerebrovascular/efeitos dos fármacos , Histamina/farmacologia , Animais , Gatos , Núcleo Caudado/efeitos dos fármacos , Núcleo Caudado/fisiologia , Líquido Cefalorraquidiano , Cimetidina/farmacologia , Histamina/administração & dosagem , Injeções Intraventriculares , Receptores Histamínicos/efeitos dos fármacos , Vasodilatação/efeitos dos fármacosRESUMO
Thromboembolic brain ischemia was produced in dogs using an autologous blood clot model. The effect of postembolic treatment with flunarizine and streptokinase on hemispheric cerebral metabolic rate for oxygen (CMRO2), oxygen extraction ratio (OER), and cerebral blood flow (CBF) was studied by positron emission tomography (oxygen-15 technique) 24 hours after the insult. We studied five groups of experimental dogs and compared them with a control group of nonembolized dogs. Group I received no treatment, Group II was treated locally with 500,000 IU streptokinase starting 30 minutes after the insult, Group III received streptokinase locally 30 minutes after the insult and 0.1 mg/kg i.v. flunarizine immediately after the insult and 2 hours later, Group IV received flunarizine as Group III, and Group V was orally pretreated with 0.5 mg/kg/day flunarizine during 2 weeks preceding embolization. Compared with the contralateral hemisphere, in the embolized hemisphere a significant reduction of CMRO2 (-25% to -40%) and CBF in normocapnia (-35%) and hypercapnia (-50%) was observed in Groups I, II, and V. In Groups III and IV, CMRO2, OER, and CBF of the embolized hemisphere were within the normal range during normocapnia and hypercapnia; the extent of the ischemic lesions was markedly less than in the other groups of experimental dogs. We conclude that flunarizine treatment after experimental thromboembolic stroke had a favorable influence on brain tissue. Chronic preventive flunarizine treatment failed to have a beneficial effect.
Assuntos
Bloqueadores dos Canais de Cálcio/uso terapêutico , Transtornos Cerebrovasculares/tratamento farmacológico , Flunarizina/uso terapêutico , Embolia e Trombose Intracraniana/complicações , Estreptoquinase/uso terapêutico , Animais , Encéfalo/metabolismo , Circulação Cerebrovascular/efeitos dos fármacos , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/fisiopatologia , Cães , Feminino , Flunarizina/sangue , Masculino , Consumo de Oxigênio/efeitos dos fármacosRESUMO
Cerebral blood flow and oxygen metabolism have been measured with the steady-state oxygen-15 technique and positron emission tomography in anesthetized dogs. Regional microembolization was induced by infusing Sephadex particles (diameter, 40 micron) into one of the common carotid arteries. In the first series of experiments, 2.5 mg Sephadex was infused, and the dogs were examined within 3-4 hours after embolization. In a second series 0.55 mg Sephadex was infused, and the dogs were examined either in the first 3-4 hours or 24-48 hours after embolization. Cerebral blood flow, oxygen extraction ratio, and cerebral oxygen utilization were measured at 3 PCO2 levels. In the acute experiments, cerebral oxygen utilization in the embolized hemisphere was 6 (0.55 mg Sephadex) and 25% (2.5 mg Sephadex) lower than on the contralateral side. While cerebral blood flow was symmetrically distributed in normocapnia and hypocapnia, it was 9 (0.55 mg Sephadex) and 35% (2.5 mg Sephadex) lower in the embolized hemisphere during hypercapnia. In normocapnia and hypocapnia the lower oxygen utilization in the embolized hemisphere was characterized by a lower oxygen extraction ratio, and in hypercapnia by an unchanged (0.55 mg Sephadex) or by a higher (2.5 mg Sephadex) extraction ratio. The different effect on oxygen extraction ratio in the control and embolized hemispheres resulted in images of uncoupling between perfusion and oxygen demand that varied according to the PCO2. The experiments also showed a fall in cerebral blood flow in the embolized hemisphere after 3-4 hours, indicating delayed hypoperfusion. After 24-48 hours, blood flow was about 10% higher in the embolized hemisphere, and this was observed at the 3 PCO2 levels, while the oxygen extraction ratio was systematically lower. Oxygen utilization in the embolized hemisphere was depressed to practically the same extent as in acute experiments. It can be concluded that between 4 and 24 hours after microembolization the cerebral microcirculation shows important changes, with installation of luxury perfusion in the face of an unchanging decreased oxygen metabolism.
Assuntos
Circulação Cerebrovascular , Embolia e Trombose Intracraniana/fisiopatologia , Consumo de Oxigênio , Tomografia Computadorizada de Emissão , Anestesia , Animais , Encéfalo/metabolismo , Cães , Feminino , Embolia e Trombose Intracraniana/diagnóstico por imagem , Embolia e Trombose Intracraniana/metabolismo , MasculinoRESUMO
BACKGROUND AND PURPOSE: Cerebral blood flow and oxygen metabolism were measured and a cerebral angiography was performed in dogs with experimental subarachnoid hemorrhage to assess the relation between arterial narrowing (vasospasm) and the fall of blood flow. Cerebral blood volume and the cerebrovascular CO2 reactivity were also measured to estimate the cerebrovascular reserve. Several groups of dogs were treated with flunarizine in different regimens to assess its possible therapeutic effect. METHODS: The experiments were performed in the three-hemorrhage canine model for subarachnoid hemorrhage. Cerebral blood flow and cerebral oxygen metabolism were measured in anesthetized (nitrous oxide) dogs using positron emission tomography in combination with the 15O steady-state method. Basilar artery diameter was evaluated by digital subtraction angiography. RESULTS: In normal dogs, cerebral blood flow, oxygen consumption, and oxygen extraction ratio were 46.4 +/- 9.0 ml/100 ml per minute, 3.65 +/- 0.76 ml/100 ml per minute, and 39.9 +/- 3.4%, respectively; basilar artery diameter was 1.33 +/- 0.25 mm. Repeated subarachnoid blood injection (3 x 5 ml) reduced basilar artery diameter to < 20% of normal (p < 0.01). Cerebral blood flow was reduced by only 25% (p < 0.001); oxygen consumption was preserved at a low normal level by a 29% compensatory increase of the oxygen extraction (p < 0.001). Cerebral blood volume and cerebrovascular CO2 reactivity remained nearly normal. Early (after the first blood injection) peroral treatment with flunarizine (0.5 mg/kg daily) resulted in less severe basilar artery narrowing (56% of normal; p < 0.05 versus untreated). However, this treatment had no effect on cerebral blood flow, blood volume, oxygen consumption, and extraction. CONCLUSIONS: The observed fall of cerebral blood flow in experimental subarachnoid hemorrhage is not related to arterial narrowing but to an increased cerebrovascular resistance at the level of the small parenchymal vessels, and the latter, in contrast to arterial narrowing, is unaffected by flunarizine.