RESUMEN
BACKGROUND AND AIMS: Some crucial associations between obesity-related altered adipokine levels and the main factors of atherosclerotic, atherothrombotic processes are not fully known. We analysed the relationships of classic adipokines, namely leptin, resistin, adiponectin, tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6) with the markers of platelet activation, including mean platelet volume (MPV), platelet surface/soluble P-selectin, platelet-derived microparticles (PMPs), the parameters of coagulation abnormalities and common carotid intima-media thickness (IMT) in obese patients with or without atherosclerotic comorbidities in comparison to age- and sex-matched controls. METHODS AND RESULTS: We enrolled 154 obese individuals, including 98 suffering from atherosclerotic concomitant conditions, 56 free of atherosclerotic comorbidities and 62 healthy controls. Plasma levels of leptin, resistin, adiponectin, TNF-α, IL-6, soluble P-selectin, and plasminogen activator inhibitor-1 antigen (PAI-1 ag) were analysed by ELISA. Platelet surface P-selectin and PMPs were measured by flow cytometry. IMT was detected by ultrasonography. Adipokines were closely associated with markers of platelet hyperactivity, hypercoagulability, hypofibrinolysis and IMT. Significant independent associations were found between leptin and platelet count (p < 0.0001), MPV (p = 0.019), PMPs (p < 0.0001), fibrinogen (p = 0.001), factor VIII (FVIII) activity (p = 0.035); adiponectin and PAI-1 ag (p = 0.035); resistin and soluble P-selectin (p = 0.002); TNF-α and PAI-1 ag (p < 0.0001); and IL-6 and fibrinogen (p = 0.011). Finally, leptin (p = 0.0005), adiponectin (p = 0.019), IL-6 (p = 0.001), MPV (p = 0.0003), PMP (p = 0.008), and FVIII activity (p = 0.043) were independent predictors of IMT. CONCLUSION: Overall, we suggest that in obese subjects altered adipokine levels play a key role in common carotid atherosclerosis both directly and through haemostatic parameters.
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Adipoquinas/sangre , Aterosclerosis/sangre , Plaquetas/metabolismo , Enfermedades de las Arterias Carótidas/sangre , Arteria Carótida Común/diagnóstico por imagen , Grosor Intima-Media Carotídeo , Hemostasis , Obesidad/sangre , Trombosis/sangre , Adulto , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/etiología , Biomarcadores/sangre , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/etiología , Estudios de Casos y Controles , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Obesidad/diagnóstico , Activación Plaquetaria , Factores de Riesgo , Trombosis/diagnóstico por imagen , Trombosis/etiologíaRESUMEN
The potential of multiparametric MRI parameters for differentiating between reversibly and irreversibly damaged brain tissue was investigated in an experimental model of focal brain ischemia in the rat. The middle cerebral artery (MCA) was occluded by intraluminal suture insertion for 60 or 90 min, followed by 4.5 h of reperfusion. The apparent diffusion coefficient (ADC) of brain water, T(1) and T(2) relaxation times, and CBF(i), an MR-derived index of cerebral perfusion, were repeatedly measured and correlated with the outcome from the ischemic impact. A novel user-independent approach for segmentation of ADC maps into classes of increasing injury was introduced to define regions of interest (ROIs) in which these parameters were evaluated. MCA occlusion led to a graded decline of ADC, which corresponded with both the severity of flow reduction and an increase in T(1) and T(2) relaxation times. Removal of the suture led to a triphasic restitution of blood flow consisting of a fast initial rise, a secondary decline, and final normalization. Postischemic reperfusion led to a rise of ADC irrespective of the duration of ischemia. However, the quality of recovery declined with increasing severity of the ischemic impact. Throughout the observation time, T(1) and T(2) showed a continuous increase, the intensity of which correlated with the severity of ADC decline during ischemia. Particularly with longer ischemia time, elevated T(2) in combination with reduced ADC yielded a lower probability of recovery during recirculation, while intraischemic perfusion information contributed less to the prediction of outcome. In conclusion, the combination of MR parameters at the end of ischemia correlated with the probability of tissue recovery but did not permit reliable differentiation between reversibly and irreversibly damaged tissue.
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Encéfalo/patología , Ataque Isquémico Transitorio/patología , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Animales , Circulación Cerebrovascular , Masculino , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Disturbances of coagulation and fibrinolytic pathways were studied in 53 young patients with cerebral ischemia. Upon admission 26 of 53 patients had abnormality in at least one of the antithrombin-III, protein C, protein S activities or in activated protein C (APC) ratios. Three months after the first examination the majority of the previously detected abnormalities returned to normal values and the most frequent alterations were decrease in protein S activity (3 patients) and APC resistance (3 patients). Conditions resulting in impaired fibrinolysis were frequently detected upon admission. Elevation of plasminogen activator inhibitor-1, lipoprotein (a), and alpha-2-antiplasmin was present in 23, 10, and 4 cases, respectively. It is concluded that abnormalities of coagulation as well as of the fibrinolytic systems are prevalent in the acute phase of cerebral ischemia, however, the results may be significantly influenced by the disease process or the acute phase effect.
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Isquemia Encefálica/epidemiología , Isquemia Encefálica/fisiopatología , Fibrinólisis , Trombofilia/epidemiología , Trombofilia/fisiopatología , Enfermedad Aguda , Adolescente , Adulto , Edad de Inicio , Antitrombina III/metabolismo , Trastornos de la Coagulación Sanguínea/complicaciones , Trastornos de la Coagulación Sanguínea/epidemiología , Trastornos de la Coagulación Sanguínea/fisiopatología , Isquemia Encefálica/etiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Proteína C/metabolismo , Proteína S/metabolismo , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/fisiopatología , Trombofilia/complicacionesRESUMEN
Mice were subjected to 60 min occlusion of the left middle cerebral artery (MCA) followed by 1-6 h of reperfusion. Tissue samples were taken from the MCA territory of both hemispheres to analyse ischaemia-induced changes in the phosphorylation of the initiation factor eIF-2alpha, the elongation factor eEF-2 and p70 S6 kinase by western blot analysis. Tissue sections from additional animals were taken to evaluate ischaemia-induced changes in global protein synthesis by autoradiography and changes in eIF-2alpha phosphorylation by immunohistochemistry. Transient MCA occlusion induced a persistent suppression of protein synthesis. Phosphorylation of eIF-2alpha was slightly increased during ischaemia, it was markedly up-regulated after 1 h of reperfusion and it normalized after 6 h of recirculation despite ongoing suppression of protein synthesis. Similar changes in eIF-2alpha phosphorylation were induced in primary neuronal cell cultures by blocking of endoplasmic reticulum (ER) calcium pump, suggesting that disturbances of ER calcium homeostasis may play a role in ischaemia-induced changes in eIF-2alpha phosphorylation. Dephosphorylation of eIF-2alpha was not paralleled by a rise in levels of p67, a glycoprotein that protects eIF-2alpha from phosphorylation, even in the presence of active eIF-2alpha kinase. Phosphorylation of eEF-2 rose moderately during ischaemia, but returned to control levels after 1 h of reperfusion and declined markedly below control levels after 3 and 6 h of recirculation. In contrast to the only short-lasting phosphorylation of eIF-2a and eEF-2, transient focal ischaemia induced a long-lasting dephosphorylation of p70 S6 kinase. The results suggest that blocking of elongation does not play a major role in suppression of protein synthesis induced by transient focal cerebral ischaemia. Investigating the factors involved in ischaemia-induced suppression of the initiation step of protein synthesis and identifying the underlying mechanisms may help to further elucidate those disturbances directly related to the pathological process triggered by transient cerebral ischaemia and leading to neuronal cell injury.
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Corteza Cerebral/metabolismo , Factor 2 Eucariótico de Iniciación/metabolismo , Ataque Isquémico Transitorio/metabolismo , Neuronas/metabolismo , Factor 2 de Elongación Peptídica/metabolismo , Proteínas Quinasas S6 Ribosómicas/metabolismo , Animales , Células Cultivadas , Corteza Cerebral/irrigación sanguínea , Corteza Cerebral/citología , Circulación Cerebrovascular , Inhibidores Enzimáticos/farmacología , Immunoblotting , Inmunohistoquímica , Flujometría por Láser-Doppler , Ratones , Arteria Cerebral Media/cirugía , Neuronas/efectos de los fármacos , Fosforilación , Biosíntesis de Proteínas , Ratas , Ratas Wistar , Tapsigargina/farmacologíaRESUMEN
Applying the recently developed DNA array technique to a murine stroke model, we found that the gene coding for RhoB, a member of the family of GTPases that regulate a variety of signal transduction pathways, is upregulated in ischemia-damaged neurons. RhoB immunoreactivity precedes DNA single-strand breaks and heralds the evolving infarct, making it an early predictor of neuronal death. Expression of RhoB colocalized with drastic rearrangement of the actin cytoarchitecture indicates a role for Rho in postischemic morphological changes. Apoptosis in a murine hippocampal cell line was also associated with an early increase in RhoB protein. Activation of caspase-3, a crucial step in apoptosis, could be inhibited by cytochalasin D, a substance that counteracts the actin-modulating activity of Rho GTPases, indicating that Rho proteins may have impact on injury-initiated neuronal signal transduction. Our findings make Rho GTPases potential targets for the development of drugs aimed at limiting neuronal death following brain damage.
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Apoptosis/fisiología , Infarto Encefálico/enzimología , Isquemia Encefálica/enzimología , Degeneración Nerviosa/enzimología , Daño por Reperfusión/enzimología , Regulación hacia Arriba/genética , Proteína de Unión al GTP rhoB/metabolismo , Citoesqueleto de Actina/efectos de los fármacos , Citoesqueleto de Actina/enzimología , Citoesqueleto de Actina/patología , Animales , Apoptosis/genética , Infarto Encefálico/genética , Infarto Encefálico/fisiopatología , Isquemia Encefálica/genética , Isquemia Encefálica/fisiopatología , Caspasa 3 , Caspasas/efectos de los fármacos , Caspasas/metabolismo , Células Cultivadas/enzimología , Células Cultivadas/patología , Citocalasina D/farmacología , Daño del ADN/genética , ADN de Cadena Simple/genética , Modelos Animales de Enfermedad , Expresión Génica/fisiología , Hipocampo/enzimología , Hipocampo/patología , Hipocampo/fisiopatología , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Degeneración Nerviosa/genética , Degeneración Nerviosa/fisiopatología , Neuronas/enzimología , Neuronas/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Valor Predictivo de las Pruebas , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Daño por Reperfusión/genética , Daño por Reperfusión/fisiopatología , Factores de Tiempo , Proteína de Unión al GTP rhoB/genéticaRESUMEN
Changes in apparent diffusion coefficients (ADC) were compared with alterations of adenosine triphosphate (ATP) concentration and pH in different phases of transient focal cerebral ischemia to study the ADC threshold for breakdown of energy metabolism and tissue acidosis during ischemia and reperfusion. Male Wistar rats underwent 1 hour of middle cerebral artery occlusion without recirculation (n = 3) or with 1 hour (n = 4) or 10 hours of reperfusion (n=5) inside the magnet, using a remotely controlled thread occlusion model. ADC maps were calculated from diffusion-weighted images and normalized to the preischemic value to obtain relative ADC maps. Hemispheric lesion volume (HLV) was determined on the last relative ADC maps at different relative ADC thresholds and was compared to the HLV measured by ATP depletion and by tissue acidosis. The HLVs, defined by ATP depletion and tissue acidosis, were 26.0% +/- 10.6% and 38.1% +/- 6.5% at the end of ischemia, 3.3% +/- 2.4% and 4.8% +/- 3.5% after 1 hour of reperfusion, and 11.2% +/- 4.7% and 10.9% +/- 5.2% after 10 hours of recirculation, respectively. The relative ADC thresholds for energy failure were consistently approximately 77% of the control value in the three different groups. The threshold for tissue acidosis was higher at the end of ischemia (86% of control) but was similar to the results obtained for ATP depletion after 1 hour (78% of control) and 10 hours (76% of control) of recirculation. These results indicate that the described relative ADC threshold of approximately 77% of control provides a good estimate for the breakdown of energy metabolism not only during middle cerebral artery occlusion but also at the early phase of reperfusion, when recovery of energy metabolism is expected to occur, or some hours later, when development of secondary energy failure was described.
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Encéfalo/metabolismo , Metabolismo Energético/fisiología , Ataque Isquémico Transitorio/metabolismo , Daño por Reperfusión/metabolismo , Acidosis/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Encéfalo/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Masculino , Ratas , Ratas WistarRESUMEN
A systematic investigation was carried out for the improvement of the prompt gamma interrogation method used for contraband detection by the pulsed fast/thermal neutron analysis (PFTNA) technique. Optimizations of source detector shielding and geometry, role of the type and dimension of the gamma detector, attenuation of neutrons and gamma rays in bulky samples were also studied. Results obtained for both the shielding materials and elemental content of cocaine simulants have been compared with the values calculated by the MCNP-4A code.
Asunto(s)
Cocaína/análisis , Rayos gamma , Drogas Ilícitas , Explosiones/prevención & control , Análisis de Activación de Neutrones/métodos , Protección Radiológica , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Neutron spectra behind iron slabs of different thicknesses have been measured in the energy range from 1.6 to 14 MeV using a proton recoil spectrometer and 2H(d, n)3He and 9Be(d, n)10B neutron sources. The measured results have been compared with the predicted ones using the three dimensional Monte Carlo code MCNP 4A and pointwise cross sections from the ENDF/B-IV and ENDF/B-VI data files. The results show that the ENDF/B-IV calculations are in better agreement with the experiment than those obtained by using the ENDF/B-VI cross section data.
RESUMEN
The aim of the present work was to investigate the impact of gender on resting cerebral blood flow velocity and cerebrovascular reserve capacity among diabetic patients. Middle cerebral artery mean blood flow velocity (MCAV) was measured in 72 patients suffering from type 1 diabetes mellitus at rest and 5, 10, 15 and 20 min after intravenous administration of 1 g acetazolamide. Cerebrovascular reserve was calculated as the maximal percent increase in MCAV after acetazolamide. Resting MCAV and cerebrovascular reserve capacity were compared between males and females. Resting cerebral blood flow velocity was higher in diabetic females than in males (men, 55.0+/-17.0 cm/s; women, 64.4+/-12.6 cm/s, p=0.0094). Cerebrovascular reserve capacity was similar in diabetic women and men (men, 44.0%+/-18.6%; women, 52.6%+/-32.9%, p=0.17). Comparing MCAV and cerebrovascular reserve capacity among the diabetic subgroups with disease duration < or = 10 years and >10 years, we did not detect any differences between women and men. Duration of diabetes was an important factor in determining cerebrovascular reserve capacity in both sexes: long-term diabetic women and men showed lower CRC values than diabetics with < or = 10 years disease duration. Cerebrovascular reserve capacity is similar in diabetic women and men. Taking into consideration that cerebrovascular reserve is normally higher among women, our finding indicates a relatively more serious worsening of cerebral vasodilatory responses in women suffering from type 1 diabetes.
Asunto(s)
Acetazolamida/farmacología , Circulación Cerebrovascular/efectos de los fármacos , Diabetes Mellitus Tipo 1/fisiopatología , Caracteres Sexuales , Sistema Vasomotor/efectos de los fármacos , Sistema Vasomotor/fisiopatología , Adulto , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Diabetes Mellitus Tipo 1/diagnóstico por imagen , Femenino , Humanos , Masculino , Ultrasonografía , Sistema Vasomotor/diagnóstico por imagenRESUMEN
Perfusion-weighted imaging (PWI), using the method of arterial spin tagging, is strongly T(1)-dependent. This translates into a high field dependency of the perfusion signal intensity. In order to determine the expected signal improvement at higher magnetic fields we compared perfusion-weighted images in rat brain at 4.7 T and 7 T. Application of PWI to focal ischemia and functional activation of the brain and the use of two different anesthetics allowed the observation of a wide range of flow values. For all these (patho-)physiological conditions switching from 4.7 T to 7 T resulted in a significant increase of mean perfusion signal intensity by a factor of 2.96. The ratio of signal intensities of homotopic regions in the ipsi- and contralateral hemisphere was field-independent. The relative contribution of a) T(1) relaxation time, b) net magnetization, c) the Q-value of the receiver coils and d) the degree of adiabatic inversion to the signal improvement at higher field strength were discussed. It was shown that the main parameters contributing to the higher signal intensity are the lengthening of T(1) and the higher magnetization at the higher magnetic field.
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Isquemia Encefálica/patología , Circulación Cerebrovascular , Imagen por Resonancia Magnética/métodos , Animales , Estimulación Eléctrica , Miembro Anterior , Procesamiento de Imagen Asistido por Computador , Magnetismo , Masculino , Ratas , Ratas Wistar , Flujo Sanguíneo Regional , Corteza Somatosensorial/irrigación sanguínea , Corteza Somatosensorial/patología , Marcadores de SpinRESUMEN
Recent investigations on transient focal cerebral ischemia suggested recovery of energy metabolism during early reperfusion, but followed by secondary energy failure. As disturbances of energy metabolism are reflected by changes of the apparent diffusion coefficient (ADC) of water, the aim of the current study was to follow the dynamics of the ADC during 1 hour of middle cerebral artery occlusion (MCAO) and 10 hours of reperfusion. The right MCA was occluded in male Wistar rats inside the magnet using a remotely controlled thread occlusion model. Diffusion-, perfusion-, and T2-weighted images were performed repetitively, and ADC, perfusion, and T2 maps were calculated and normalized to the respective preischemic value. The lesion volume at each time point was defined by ADC < 80% of control. At the end of 1-hour MCAO the hemispheric lesion volume was 22.3 +/- 9.0%; it decreased to 6.4 +/- 5.7% in the first 2 hours of reperfusion (P < 0.01), but then increased again, and by the end of 10 hours of reperfusion reached 17.3 +/- 9.3%. The mean relative ADC in the end ischemic lesion volume significantly improved within 2 hours of reperfusion (from 65.7 +/- 1.2% to 90.1 +/- 6.7% of control), but later declined and decreased to 75.4 +/- 7.3% of control by the end of the experiment. Pixels with secondary deterioration of ADC showed a continuous increase of T2 value during the first 2 hours of reperfusion in spite of ADC improvement, indicating improving cytotoxic, but generation of vasogenic edema during early reperfusion. A significant decrease of the perfusion level was not observed during 10 hours of recirculation. The authors conclude that the improvement of ADC in the early phase of reperfusion may be followed by secondary deterioration that was not caused by delayed hypoperfusion.
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Ataque Isquémico Transitorio/metabolismo , Animales , Difusión , Ataque Isquémico Transitorio/diagnóstico , Imagen por Resonancia Magnética/métodos , Masculino , Ratas , Ratas Wistar , Daño por Reperfusión/diagnóstico , Daño por Reperfusión/metabolismo , Factores de TiempoRESUMEN
It has been proposed that NAD depletion resulting from excessive activation of poly(ADP-ribose) polymerase is responsible for secondary energy failure after transient cerebral ischemia. However, this hypothesis has never been verified by measurement of ATP and NAD levels in the same tissue sample. In this study, we therefore investigated the effect of transient focal cerebral ischemia on the temporal profiles of changes in the levels of energy metabolites and NAD. Ischemia was induced in mice by occluding the left middle cerebral artery using the intraluminal filament technique. Animals were subjected to 1-h ischemia, followed by 0, 1, 3, 6, or 24 h of reperfusion. During ischemia, ATP levels, total adenylate pool, and adenylate energy charge dropped to approximately 20, 50, and 40% of control, respectively, whereas NAD levels remained close to control. Energy state recovered transiently, peaking at 3 h of recovery (ATP levels and total adenylate pool recovered to 78 and 81% of control). In animals subjected to reperfusion of varying duration, the extent of ATP depletion was clearly more pronounced than that of NAD. The results imply that depletion of NAD pools did not play a major role in secondary disturbances of energy-producing metabolism after transient focal cerebral ischemia. Changes in ATP levels were closely related to changes in total adenylate pool (p<0.001). The high energy charge after 6 h of reperfusion (0.90 versus a control value of 0.93) and the close relationship between the decline of ATP and total adenylate pool suggest that degradation or a washout of adenylates (owing to leaky membranes) rather than a mismatch between energy production and consumption is the main causative factor contributing to the secondary energy failure observed after prolonged recovery.
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Encéfalo/metabolismo , Metabolismo Energético , Ataque Isquémico Transitorio/metabolismo , NAD/metabolismo , Adenosina Monofosfato/metabolismo , Adenosina Trifosfato/metabolismo , Animales , Encéfalo/irrigación sanguínea , Modelos Animales de Enfermedad , Fluorescencia , Mediciones Luminiscentes , Masculino , Ratones , Ratones Endogámicos C57BL , Especificidad de Órganos , Poli(ADP-Ribosa) Polimerasas/metabolismoRESUMEN
BACKGROUND AND PURPOSE: CO(2) response was examined in rats undergoing 60 minutes of middle cerebral artery occlusion (MCAO) and 4.5 hours of reperfusion. Because it is not clear whether the vasoreactivity improves during reperfusion in parallel with tissue recovery, CO(2) response was determined spatially resolved, sequentially in the initially ischemic but later recovered areas and in the permanently damaged areas. METHODS: Apparent diffusion coefficient (ADC) maps were calculated from diffusion-weighted images, whereas CO(2) reactivity maps were determined from the difference in perfusion signal intensity before and after CO(2) stimulation. CO(2) reactivity (administration of 6% CO(2) for 5 minutes) was expressed in % change of perfusion signal intensity/mm Hg of PCO(2) increase. ATP levels of tissue were used as a measure of outcome. The recovered and permanently damaged tissues were differentiated by combined use of end-ischemic ADC map and ATP image at the end of the experiment. RESULTS: The preischemic (control) CO(2) reactivity of 3.5+/-0.9%/mm Hg decreased dramatically during MCAO in the ischemic hemisphere. During reperfusion, it remained <1%/mm Hg in the region with end-ischemic ADC <80% of the preischemic control value, but showed gradual recovery in the region with end-ischemic ADC >80% of control. Although at the end of the experiment the CO(2) reactivity was significantly higher in the recovered tissue than in the permanently damaged tissue (1.15+/-0.44 and 0.13+/-0.47%/mm Hg, respectively; P:<0.01), it still remained far below the normal control value (P:<0.01). CONCLUSIONS: The noninvasive perfusion-weighted MR imaging in combination with a CO(2) challenge permits the investigation of the spatially resolved vascular reactivity during a longitudinal study of cerebral ischemia. Our data suggest that severe ischemia is followed by a prolonged disturbance of CO(2) reactivity, despite already normalized energy metabolism.
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Isquemia Encefálica/metabolismo , Dióxido de Carbono/metabolismo , Adenosina Trifosfato/análisis , Animales , Isquemia Encefálica/patología , Dióxido de Carbono/análisis , Dióxido de Carbono/farmacología , Difusión , Metabolismo Energético , Mediciones Luminiscentes , Imagen por Resonancia Magnética/métodos , Masculino , Arteria Cerebral Media/metabolismo , Putamen/metabolismo , Putamen/patología , Ratas , Ratas Wistar , Reperfusión , Factores de TiempoRESUMEN
Cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity acceleration can be easily and reliably assessed by measuring acetazolamide-induced changes using transcranial Doppler. The authors' aim was to determine whether there are gender-related differences in these parameters. Fifty-six healthy subjects (27 males, 29 females) were examined using transcranial Doppler. Velocities in the middle cerebral artery on both sides were recorded before and at 5, 10, 15, and 20 minutes after intravenous administration of 1 g acetazolamide. The baseline mean flow velocity in the middle cerebral artery was significantly higher in women than in men (p < 0.02). After acetazolamide administration, significantly higher cerebrovascular reactivity, cerebrovascular reserve capacity, and velocity acceleration were observed in females than in males (p < 0.001 in all cases). Subgroup analysis showed that women before menopause responded with higher cerebrovascular reserve capacity and velocity acceleration than age-matched men (p < 0.01 and p < 0.001, respectively), but no significant difference was found between females after menopause and men of similar age.
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Acetazolamida , Encéfalo/irrigación sanguínea , Inhibidores de Anhidrasa Carbónica , Ultrasonografía Doppler Transcraneal , Vasodilatación/efectos de los fármacos , Adulto , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores SexualesRESUMEN
Autoradiographic measurement of local cerebral blood flow (CBF) with [14C]iodoantipyrine (IAP) is limited in mice by the difficulty in cannulating vessels and the blood loss for repeated blood sampling. The authors modified and validated the method to measure local CBF with [14C]IAP in mice by combining intraperitoneal tracer application with a single blood sampling from the heart at the end of the experiment. Experiments were carried out in male SV129 mice under halothane anesthesia. After intraperitoneal administration of 15 microCi [14C]IAP, arterial blood samples were collected repeatedly and anesthetized animals were immersed in liquid nitrogen. In addition, frozen blood from the heart was sampled to obtain the final blood [14C]radioactivity. Correlation analysis between the sampling time and [14C]radioactivity of the arterial blood revealed a highly significant linear relationship (P < 0.001, r = 0.978) and a lag time of the [14C]tracer in arterial blood of 3.3 +/- 0.6 seconds. [14C]radioactivity of the final arterial blood sample (444 +/- 264 nCi/mL) was almost equal to that of the heart blood (454 +/- 242 nCi/mL), and the absolute difference in each animal was 3.3 +/- 4.2% (mean +/- SD). The convolution integrals for the CBF calculation were determined either by integrating the radioactivity of individual arterial blood samples or by assuming a linear rise from [14C]tracer lag time after intraperitoneal [14C]IAP injection to the value measured in the blood sample from the frozen heart. Regional flow values calculated by the two methods differed by less than 11% (not significant). This method allows the quantitative measurement of local CBF in anesthetized mice without any vessel catheterization and will make mutant mice a more powerful tool to elucidate the molecular mechanisms of brain injuries by combining flow studies with molecular-biological methods.
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Antipirina/análogos & derivados , Circulación Cerebrovascular , Manejo de Especímenes/métodos , Animales , Antipirina/administración & dosificación , Antipirina/sangre , Autorradiografía , Radioisótopos de Carbono/sangre , Vasos Coronarios , Inyecciones Intraperitoneales , Masculino , RatonesRESUMEN
Quantitative imaging contrast is evaluated which allows the selective measurement of the blood oxygenation state during cerebral ischemia within a multiparametric imaging study on rats. In a first step, the ambiguities arising in T*(2)-weighted images due to T*(2) heterogeneity are eliminated by calculating T*(2) maps. Then, 1/T'(2) maps are calculated according to 1/T'(2) = 1/T*(2) - 1/T(2) to eliminate nonsusceptibility-induced changes of 1/T*(2) after the induction of stroke. This is of particular importance in the presence of vasogenic edema. The changes Delta(1/T'(2)) after the onset of ischemia selectively quantify the variations of the deoxyhemoglobin content during the development of the infarct. The presented results are not available from conventionally recorded parameters of a stroke study and, together with perfusion-weighted images, form a powerful combination to analyze the oxygen consumption and the metabolism of the tissue. Magn Reson Med 42:1027-1032, 1999.
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Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Espectroscopía de Resonancia Magnética , Oxígeno/sangre , Animales , Edema Encefálico/metabolismo , Masculino , Consumo de Oxígeno , Ratas , Ratas Sprague-DawleyRESUMEN
The authors studied whether haemostatic abnormalities connected with the development of cerebral circulatory disturbances can be demonstrated in young stroke patients in whom Doppler and angiographic examination failed to reveal deviations indicative of stroke. They determined the in vivo activation of the coagulation system (TAT, F 1 + 2), the degree of secondary fibrinolysis (D-dimer), the plasma levels of the markers of fibrinolysis, with special regard to inhibitors: plasminogen activator inhibitor (PAI-1), alpha 2 antiplasmin (alpha 2 AP), alpha 2 macroglobulin (alpha 2 M), the frequency of pathologic serum lipoprotein (a)-Lp(a)-values and the association of PAI-1 and Lp(a) with the fibrinolytic system. They conclude that in the acute phase of the disease, the TAT and F 1 + 2 values were significantly elevated compared to the control, without change in the D-dimer value. The results suggest that in the tested period increased thrombin generation dominated and it significantly surpassed plasmin activity since the D-dimer values of that period did not indicate substantial increase in secondary fibrinolysis. The results of the study were separately analyzed in acute, chronic TIA and stroke groups. In the TIA and acute group the F 1 + 2 values, while in stroke the TAT values were more elevated. The in vitro fibrinolytic capacity of the patients significantly decreased compared to controls, showing significant correlation with the Lp(a) level, but not with the PAI value. Examination of the marker molecules renders possible to assess the degree of hypercoaguability and of endogenous lysis. Their knowledge is held important for judging the progression of the disease and the therapeutic consequences.
Asunto(s)
Antifibrinolíticos/uso terapéutico , Isquemia Encefálica/etiología , Trastornos Cerebrovasculares/etiología , Hemostasis , Adulto , Trastornos de la Coagulación Sanguínea/tratamiento farmacológico , Trastornos de la Coagulación Sanguínea/etiología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Trastornos Cerebrovasculares/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiologíaRESUMEN
Activation of blood coagulation and fibrinolysis has previously been detected in stroke patients. It is unknown, however, what factors contribute to the acceleration of coagulation reactions, especially in cases where no obvious predisposing factors exist. We therefore postulated and tested the hypothesis that in such patients monocytes may trigger the pathway leading to thrombosis by expressing tissue factor (TF). TF antigen was determined in 48 patients and 40 controls by flow cytometry using an indirect immunofluorescent technique. TF antigen expression was significantly increased on monocytes in young stroke patients in both the acute (p < 0.01) and chronic (p < 0.05) phases of the disease. The TF antigen also possessed functional activity, quantitated by a one-stage clotting assay. TF expression on monocytes was not associated with an elevation in C-reactive protein values. In both acute and chronic phases, blood coagulation activation markers, e.g. the thrombin-antithrombin complex and F1 + 2 fragments, were significantly elevated. However, in the acute phase D-dimer levels were similar to those in controls and were only elevated in the chronic phase of the disease (p < 0.05). In conclusion, in cerebral ischemia TF expression on monocytes suggests enhanced activation of blood coagulation and subsequent fibrinolysis.
Asunto(s)
Ataque Isquémico Transitorio/sangre , Monocitos/metabolismo , Tromboplastina/metabolismo , Adolescente , Adulto , Biomarcadores/sangre , Coagulación Sanguínea/fisiología , Estudios de Casos y Controles , Femenino , Fibrinolisina/biosíntesis , Fibrinólisis/fisiología , Humanos , Masculino , Persona de Mediana Edad , Trombina/biosíntesisRESUMEN
AIMS: Strokes caused by hemodynamically significant internal carotid artery stenoses and occlusions are believed to be embolic or hemodynamic of origin. The aim of the study was to assess cerebral hemodynamic compromises of significant carotid artery stenosis of occlusion using vasodilatory testing (acetazolamide test) in asymptomatic and symptomatic patients. PATIENTS AND METHODS: 36 patients with unilateral, hemodynamically significant carotid stenosis were investigated using transcranial Doppler acetazolamide-test. There were 12 asymptomatic and 24 symptomatic patients. The middle cerebral artery mean blood flow velocity was measured at rest and after intravenous injection of 1 g acetazolamide. The absolute mean blood flow velocities and the cerebrovascular reactivity was compared at the stenotic and non-stenotic side. In a further analysis the mean velocities and the cerebrovascular reactivity values of the stenotic side were compared. Results of acetazolamide test performed on 28 healthy volunteers were used as control values. RESULTS: There were no side-differences between the middle cerebral artery mean blood flow velocity and cerebrovascular reactivity values in the asymptomatic group. In the symptomatic group, however middle cerebral artery mean velocity and cerebrovascular reactivity after acetazolamide was significantly lower on the stenotic side, than on the non-stenotic one. Comparing the different groups non-stenotic sides did not differ to each other in their cerebral blood flow velocity and cerebrovascular reactivity. In the symptomatic patients, however, cerebral blood flow velocity and cerebrovascular reserve capacity after acetazolamide was lower, than that of the stenotic side of asymptomatic patients and controls. CONCLUSIONS: The transcranial Doppler is a suitable method for detecting altered cerebral hemodynamics in significant carotid stenosis. Impaired cerebrovascular reactivity may refer to the impairment of cerebral autoregulatory mechanisms.
Asunto(s)
Arteriosclerosis/complicaciones , Estenosis Carotídea/complicaciones , Trastornos Cerebrovasculares/etiología , Arteriosclerosis Intracraneal/complicaciones , Acetazolamida , Arteriosclerosis/diagnóstico por imagen , Velocidad del Flujo Sanguíneo , Estenosis Carotídea/diagnóstico por imagen , Circulación Cerebrovascular , Trastornos Cerebrovasculares/diagnóstico por imagen , Humanos , Arteriosclerosis Intracraneal/diagnóstico por imagen , Ultrasonografía Doppler TranscranealRESUMEN
Changes in the diameter of intracranial arteries might have a major role in the pathophysiology of migraine. Though several studies have found alterations in velocity of blood flow and in cerebral vasomotor reactivity of intracranial arteries in migraineurs in headache-free periods, as well as during migraine attacks, the results are inconclusive. To determine if intracranial hemodynamic characteristics of patients with migraine differ from those of controls, we measured baseline velocity of blood flow by transcranial Doppler in the middle cerebral arteries in headache-free periods in 51 migraine patients and in 101 age-matched controls. Cerebrovascular reactivity was measured after intravenous administration of acetazolamide in 12 migrainous patients and in 19 controls. Baseline mean velocity was significantly higher in the migraine group (70 versus 65 and 72 versus 65 cm/s with P = 0.02 and P = 0.0007 on the left and right sides, respectively). The difference stayed significant during acetazolamide stimulation, but the course of response did not differ between controls and migraineurs. Despite statistical significance, absolute differences were small. Therefore, middle cerebral artery velocity measurements and the acetazolamide test are not useful for the diagnosis of migraine in the interictal period.