RESUMEN
OBJECTIVE: To analyze referrals from Primary Care consultation to Orthopaedic Surgery reference department. As a secondary objective, to establish 2referral scenarios in order to determine the impact of variability on referral. MATERIAL AND METHODS: Cross-sectional observational study, analyzing referrals from Primary Care to Orthopaedic Surgery during the first half of the years 2018, 2019, and 2021. The number of referrals issued by each doctor and each Primary Care Healthcare Center was examined, according to the classification of the different Basic Healthcare Zones. RESULTS: There is great variability in the number of referrals, both according to the type of Basic Healthcare Zone and by each Primary Care facultative. The referral ratios behaved uniformly over time (P<0.001). Due to a large number of referrals, 2scenarios have been constructed: In the first scenario, the referral ratio would be in the middle of the referral rate spectrum. In the second scenario, the lowest referral ratios recorded have been taken as a reference. The reduction of variability in the 2scenarios assumed provides a significant reduction in the demand for care. CONCLUSION: Reducing variability would have a beneficial effect on the capacity of the Orthopaedic Surgery service to provide care.
Asunto(s)
Traumatología , Humanos , Estudios Transversales , Atención Primaria de Salud , Derivación y ConsultaRESUMEN
OBJECTIVE: To analyse referrals from Primary Care consultation to Orthopaedic Surgery reference department. As a secondary objective, to establish 2 referral scenarios in order to determine the impact of variability on referral. MATERIAL AND METHODS: Cross-sectional observational study, analyzing referrals from Primary Care to Orthopaedic Surgery during the first half of the years 2018, 2019, and 2021. The number of referrals issued by each doctor and each Primary Care Healthcare Center was examined, according to the classification of the different Basic Healthcare Zones. RESULTS: There is great variability in the number of referrals, both according to the type of Basic Healthcare Zone and by each Primary Care facultative. The referral ratios behaved uniformly over time (p<0.001). Due to a large number of referrals, 2 scenarios have been constructed: In the first scenario, the referral ratio would be in the middle of the referral rate spectrum. In the second scenario, the lowest referral ratios recorded have been taken as a reference. The reduction of variability in the 2 scenarios assumed provides a significant reduction in the demand for care. CONCLUSION: Reducing variability would have a beneficial effect on the capacity of the Orthopaedic Surgery service to provide care.
Asunto(s)
Traumatología , Humanos , Estudios Transversales , Departamentos de Hospitales , Atención Primaria de Salud , Derivación y ConsultaRESUMEN
In the year 1997 Siemens introduced the virtual wedge in its accelerators. The idea was that a dose profile similar to that of a physical wedge can be obtained by moving one of the accelerator jaws at a constant speed while the dose rate is changing. This work explores the observed behaviour of virtual wedge factors. A model is suggested which takes into account that at any point in time, when the jaw moves, the dose at a point of interest in the phantom is not only due to the direct beam. It also depends on the scattered radiation in the phantom, the head scatter and the behaviour of the monitoring system of the accelerator. Measurements are performed in a Siemens Primus accelerator and compared to the model predictions. It is shown that the model agrees reasonably well with measurements spanning a wide range of conditions. A strong dependence of virtual wedge factors on the dosimetric board has been confirmed and an explanation has been given on how the balance between different contributions is responsible for virtual wedge factors values.
Asunto(s)
Artefactos , Radiometría/métodos , Dosificación Radioterapéutica , Radioterapia Conformacional , Reproducibilidad de los Resultados , IncertidumbreRESUMEN
Objetivo: Analizar las derivaciones dirigidas desde Atención Primaria a Cirugía Ortopédica y Traumatología. Como objetivo secundario, establecer 2escenarios de derivación, con el fin de conocer el impacto de la variabilidad en la derivación. Material y métodos: Estudio observacional de carácter transversal de análisis de las derivaciones de Atención Primaria a Cirugía Ortopédica y Traumatología durante el primer semestre de los años 2018, 2019 y 2021. Se ha examinado el número de derivaciones que emite cada facultativo y cada centro de salud de Atención Primaria, atendiendo a la clasificación de las distintas zonas básicas de salud. Resultados: Existe una gran variabilidad en el número de derivaciones, tanto según el tipo de zona básica de salud (p < 0,001) como por cada facultativo (p < 0,001). Las ratios de derivación se comportan de forma uniforme en el tiempo (p < 0,001). Debido al alto número de derivaciones, se han construido dosescenarios: en el primero de ellos la ratio de derivación se situaría en la zona media del espectro de la tasa de derivación. En el segundo escenario, se han tomado como referencia las menores ratios de derivación registradas. La reducción de la variabilidad en los 2escenarios supuestos proporciona una disminución importante de la demanda asistencial. Conclusiones: La reducción de la variabilidad tendría un efecto beneficioso sobre la capacidad asistencial del servicio de Cirugía Ortopédica y Traumatología.
Objective: To analyze referrals from Primary Care consultation to Orthopaedic Surgery reference department. As a secondary objective, to establish 2referral scenarios in order to determine the impact of variability on referral. Material and methods: Cross-sectional observational study, analyzing referrals from Primary Care to Orthopaedic Surgery during the first half of the years 2018, 2019, and 2021. The number of referrals issued by each doctor and each Primary Care Healthcare Center was examined, according to the classification of the different Basic Healthcare Zones. Results: There is great variability in the number of referrals, both according to the type of Basic Healthcare Zone and by each Primary Care facultative. The referral ratios behaved uniformly over time (P<0.001). Due to a large number of referrals, 2scenarios have been constructed: In the first scenario, the referral ratio would be in the middle of the referral rate spectrum. In the second scenario, the lowest referral ratios recorded have been taken as a reference. The reduction of variability in the 2scenarios assumed provides a significant reduction in the demand for care. Conclusion: Reducing variability would have a beneficial effect on the capacity of the Orthopaedic Surgery service to provide care.(AU)
Asunto(s)
Humanos , Masculino , Femenino , Atención Primaria de Salud , Derivación y Consulta , Salud Pública , Salud Urbana , Salud Rural , Calidad de la Atención de Salud , Traumatología , Ortopedia , Estudios TransversalesRESUMEN
Objetivo: Analizar las derivaciones dirigidas desde Atención Primaria a Cirugía Ortopédica y Traumatología. Como objetivo secundario, establecer 2escenarios de derivación, con el fin de conocer el impacto de la variabilidad en la derivación. Material y métodos: Estudio observacional de carácter transversal de análisis de las derivaciones de Atención Primaria a Cirugía Ortopédica y Traumatología durante el primer semestre de los años 2018, 2019 y 2021. Se ha examinado el número de derivaciones que emite cada facultativo y cada centro de salud de Atención Primaria, atendiendo a la clasificación de las distintas zonas básicas de salud. Resultados: Existe una gran variabilidad en el número de derivaciones, tanto según el tipo de zona básica de salud (p < 0,001) como por cada facultativo (p < 0,001). Las ratios de derivación se comportan de forma uniforme en el tiempo (p < 0,001). Debido al alto número de derivaciones, se han construido dosescenarios: en el primero de ellos la ratio de derivación se situaría en la zona media del espectro de la tasa de derivación. En el segundo escenario, se han tomado como referencia las menores ratios de derivación registradas. La reducción de la variabilidad en los 2escenarios supuestos proporciona una disminución importante de la demanda asistencial. Conclusiones: La reducción de la variabilidad tendría un efecto beneficioso sobre la capacidad asistencial del servicio de Cirugía Ortopédica y Traumatología.
Objective: To analyze referrals from Primary Care consultation to Orthopaedic Surgery reference department. As a secondary objective, to establish 2referral scenarios in order to determine the impact of variability on referral. Material and methods: Cross-sectional observational study, analyzing referrals from Primary Care to Orthopaedic Surgery during the first half of the years 2018, 2019, and 2021. The number of referrals issued by each doctor and each Primary Care Healthcare Center was examined, according to the classification of the different Basic Healthcare Zones. Results: There is great variability in the number of referrals, both according to the type of Basic Healthcare Zone and by each Primary Care facultative. The referral ratios behaved uniformly over time (P<0.001). Due to a large number of referrals, 2scenarios have been constructed: In the first scenario, the referral ratio would be in the middle of the referral rate spectrum. In the second scenario, the lowest referral ratios recorded have been taken as a reference. The reduction of variability in the 2scenarios assumed provides a significant reduction in the demand for care. Conclusion: Reducing variability would have a beneficial effect on the capacity of the Orthopaedic Surgery service to provide care.(AU)
Asunto(s)
Humanos , Masculino , Femenino , Atención Primaria de Salud , Derivación y Consulta , Salud Pública , Salud Urbana , Salud Rural , Calidad de la Atención de Salud , Traumatología , Ortopedia , Estudios TransversalesRESUMEN
The expression of alpha s, alpha i1 and alpha i2 G-protein subunits measured by immunoblot increased in the rat prostate during sexual maturation, supporting their involvement in proliferation/differentiation. Northern blotting gave transcripts of 1.8 and 4 kb for alpha s, 1.4 and 4.5 kb (mainly) for alpha i1, and 2.4 kb for alpha i2 with levels suggesting a differential regulation (at transcription or post-transcription for alpha s, transcription for alpha i1, and translation for alpha i2). The stimulatory effects of forskolin, vasoactive intestinal peptide (VIP) and isoproterenol on adenylyl cyclase activity increased between 0.5-3 mo, remained constant up to 12 mo and decreased thereafter, conceivably following the expression of VIP and beta-adrenergic receptors. However, G-protein activation of adenylyl cyclase (by GTP and Gpp[NH]p) was maximal at 0.5 mo and then decreased as it occurred with toxin-catalyzed ADP-ribose incorporation to alpha subunits suggesting that other factors are also involved in the regulation of G-protein activity during rat prostatic development.
Asunto(s)
Adenilil Ciclasas/química , Proteínas de Unión al GTP/genética , Próstata/enzimología , Transducción de Señal/fisiología , Adenosina Difosfato Ribosa/metabolismo , Adenilil Ciclasas/metabolismo , Agonistas Adrenérgicos beta/farmacología , Factores de Edad , Animales , Northern Blotting , Colforsina/farmacología , Proteínas de Unión al GTP/química , Proteínas de Unión al GTP/metabolismo , Regulación Enzimológica de la Expresión Génica/fisiología , Guanosina Trifosfato/farmacología , Guanilil Imidodifosfato/farmacología , Isoproterenol/farmacología , Masculino , Próstata/crecimiento & desarrollo , ARN Mensajero/análisis , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Testosterona/sangre , Transcripción Genética/fisiología , Péptido Intestinal Vasoactivo/farmacologíaRESUMEN
We compare the binding properties of [125I-VIP] and [125I]-Ro 25 1553 to VPAC1 receptors, expressed in stably transfected CHO cells. [125I]-VIP labelled two VPAC1 receptor states, while [125I]-Ro 25 1553 labelled selectively a limited number of high-affinity receptors. This high-affinity state probably corresponds to an agonist-receptor-Gs ternary complex as its properties (guanyl nucleotides, EC50 values and maximal effect) were affected by cholera toxin pre-treatment. Both high- and low-affinity receptors participated in the adenylate cyclase activation. This suggested that agonists activate not only low-affinity uncoupled receptors by facilitating the ternary complex formation, but also activated the high-affinity ternary complex by accelerating the GTP binding to emptied, receptor-bound G proteins.
Asunto(s)
Péptidos Cíclicos/metabolismo , Receptores de Péptido Intestinal Vasoactivo/metabolismo , Péptido Intestinal Vasoactivo/análogos & derivados , Animales , Células CHO , Cricetinae , Guanosina Trifosfato/metabolismo , Ratas , Receptores de Péptido Intestinal Vasoactivo/agonistas , Receptores de Péptido Intestinal Vasoactivo/genética , Receptores de Tipo I del Polipéptido Intestinal Vasoactivo , Péptido Intestinal Vasoactivo/metabolismoRESUMEN
Pituitary adenylate cyclase activating peptide (PACAP) is a novel neuropeptide with regulatory and trophic functions that is related to vasoactive intestinal peptide (VIP). Here we investigate the expression of specific PACAP receptors (PAC1) and common VIP/PACAP receptors (VPAC1 and VPAC2) in the human hyperplastic prostate by immunological methods. The PAC1 receptor corresponded to a 60-KDa protein whereas the already known VPAC1 and VPAC2 receptors possessed molecular masses of 58 and 68 KDa, respectively. The heterogeneity of VIP/PACAP receptors in this tissue was confirmed by radioligand binding studies using [125I]PACAP-27 by means of stoichiometric and pharmacological experiments. At least two classes of PACAP binding sites showing different affinities could be resolved, with Kd values of 0.81 and 51.4 nM, respectively. The order of potency in displacing [125I]PACAP-27 binding was PACAP-27 approximately equal to PACAP-38 > VIP. PACAP-27 and VIP stimulated similarly adenylate cyclase activity, presumably through common VIP/PACAP receptors. The PAC1 receptor was not coupled to activation of either adenylate cyclase, nitric oxide synthase, or phospholipase C. It appears to be a novel subtype of PAC1 receptor because PACAP-27 (but not PACAP-38 or VIP) led to increased phosphoinositide synthesis, an interesting feature because phosphoinositides are involved via receptor mechanisms in the regulation of cell proliferation.
Asunto(s)
Próstata/metabolismo , Hiperplasia Prostática/metabolismo , Receptores de la Hormona Hipofisaria/metabolismo , Anciano , Anciano de 80 o más Años , Western Blotting , Humanos , Radioisótopos de Yodo , Masculino , Neuropéptidos/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa , Próstata/patología , Hiperplasia Prostática/patología , Ensayo de Unión Radioligante , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria , Receptores de la Hormona Hipofisaria/fisiología , Receptores de Péptido Intestinal Vasoactivo/análisis , Receptores de Tipo II del Péptido Intestinal Vasoactivo , Receptores de Tipo I del Polipéptido Intestinal Vasoactivo , Transducción de SeñalRESUMEN
Scanning electron microscopy (SEM) and morphometric procedures designed to survey large areas of intraparenchymal vasculature disclosed the widespread production of cerebral endothelial microvilli following global ischemia of the rat forebrain. Although these surface projections were present, they were infrequent, in sham-operated controls. As little as ten minutes of ischemia produced endothelial microvilli, which increased progressively in number with longer periods of ischemia. Transmission electron microscopy (TEM) performed on adjacent serial Vibratome sections confirmed these vascular alterations, although TEM sections did not permit an assessment of their numbers. Endothelial microvilli remained prominent in rats with up to four hours of postischemic recirculation. With SEM, these microvilli were sufficiently numerous so as to suggest that they may play a role in the development of the postischemic hypoperfusion documented by regional cerebral blood flow methods in this and other models of global cerebral ischemia.
Asunto(s)
Isquemia Encefálica/patología , Encéfalo/ultraestructura , Animales , Encéfalo/fisiopatología , Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular , Endotelio/ultraestructura , Masculino , Microscopía Electrónica , Microscopía Electrónica de Rastreo , Microvellosidades/ultraestructura , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
We studied whether small variations in intraischemic brain temperature influence the response of the blood-brain barrier (BBB) to transient forebrain global ischemia. Six animal subgroups included rats whose brain temperature was maintained at 30, 33, 36 or 39 degrees C during 20 minutes (min) of 4-vessel occlusion. Control rats without ischemia had brain temperature maintained between 30 and 39 degrees C for a 20 min period. After a 45 min postischemic recirculation period, rats were injected with the protein tracer, horseradish peroxidase (HRP), and perfusion fixed 5 or 15 min later. Control rats showed no leakage of the tracer protein. Postischemic rats in which brain temperature was controlled at either 30 or 33 degrees C failed to demonstrate consistent BBB alterations. In contrast, foci of cortical HRP extravasation were consistently documented in rats whose intraischemic brain temperature was 36 degrees C. Permeability alterations were more widespread in the 39 degrees C ischemic group and occurred in cortical, thalamic, hippocampal and striatal regions. The HRP extravasation frequently involved arterioles surrounded by perivascular spaces. Routes of increased permeability to HRP included endothelial pinocytosis, opening of the interendothelial tight junctions and diffuse leakage through damaged endothelial cells. These results demonstrate that brain temperature is a critical factor in determining whether BBB dysfunction is an acute consequence of a transient cerebral ischemic insult.
Asunto(s)
Barrera Hematoencefálica , Temperatura Corporal , Isquemia Encefálica/fisiopatología , Encéfalo/fisiopatología , Animales , Encéfalo/metabolismo , Encéfalo/ultraestructura , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Peroxidasa de Rábano Silvestre , Masculino , Ratas , Ratas Endogámicas , ReperfusiónRESUMEN
BACKGROUND AND PURPOSE: We examined the neuroprotective efficacy of moderate-dose human albumin therapy in acute focal ischemic stroke and defined the therapeutic window after stroke onset, within which this therapy would confer neurobehavioral and histopathological neuroprotection. METHODS: Sprague-Dawley rats were anesthetized with halothane/nitrous oxide and received 2-hour middle cerebral artery occlusion (MCAo) by a poly-L-lysine-coated intraluminal suture. Neurological status was evaluated during occlusion (60 minutes) and daily for 3 days after MCAo. In the dose-response study, human albumin doses of either of 0.63 or 1.25 g/kg or saline vehicle (5 mL/kg) were given intravenously immediately after suture removal. In the therapeutic window study, a human albumin dose of 1.25 g/kg was administered intravenously at 2 hours, 3 hours, 4 hours, or 5 hours after onset of MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes and brain swelling were determined. RESULTS: Moderate-dose albumin therapy significantly improved the neurological score at 24 hours, 48 hours, and 72 hours and significantly reduced total infarct volume (by 67% and 58%, respectively, at the 1.25- and 0.63-g/kg doses). Cortical and striatal infarct volumes were also significantly reduced by both doses. Brain swelling was virtually eliminated by albumin treatment. Even when albumin therapy (1.25 g/kg) was initiated as late as 4 hours after onset of MCAo, it improved the neurological score and markedly reduced infarct volumes in cortex (by 68%), subcortical regions (by 52%), and total infarct (by 61%). CONCLUSIONS: Moderate-dose albumin therapy markedly improves neurological function and reduces infarction volume and brain swelling, even when treatment is delayed up to 4 hours after onset of ischemia.
Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Fármacos Neuroprotectores/administración & dosificación , Albúmina Sérica/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Enfermedad Aguda , Animales , Conducta Animal , Encéfalo/irrigación sanguínea , Encéfalo/efectos de los fármacos , Encéfalo/patología , Edema Encefálico/etiología , Edema Encefálico/prevención & control , Isquemia Encefálica/complicaciones , Isquemia Encefálica/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Hematócrito , Humanos , Infusiones Intravenosas , Masculino , Examen Neurológico , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/patología , Resultado del TratamientoRESUMEN
The effects of antagonists of GHRH and the somatostatin analog RC-160 on the growth of OV-1063 human epithelial ovarian cancer cells xenografted into nude mice were investigated. Treatment with 20 microg/day of the GHRH antagonist JV-1-36 or MZ-5-156 and 60 microg/day of the somatostatin analog RC-160 for 25 days decreased tumor volume by 70.9% (P < 0.01), 58.3% (P < 0.05), and 60.6% (P < 0.01), respectively, vs. the control value. The levels of GH in serum were decreased in all of the treated groups, but only RC-160 significantly reduced serum insulin-like growth factor I (IGF-I). The levels of messenger ribonucleic acid (mRNA) for IGF-I and -II and for their receptors in OV-1063 tumors were investigated by multiplex RT-PCR. No expression of mRNA for IGF-I was detected, but treatment with JV-1-136 caused a 51.8% decrease (P < 0.05) in the level of mRNA for IGF-II in tumors. Exposure of OV-1063 cells cultured in vitro to GHRH, IGF-I, or IGF-II significantly (P < 0.05) stimulated cell growth, but 10(-5) mol/L JV-1-36 nearly completely inhibited (P < 0.001) OV-1063 cell proliferation. OV-1063 tumors expressed mRNA for GHRH receptors and showed the presence of binding sites for GHRH. Our results indicate that antagonistic analogs of GHRH and the somatostatin analog RC-160 inhibit the growth of epithelial ovarian cancers. The effects of RC-160 seem to be exerted more on the pituitary GH-hepatic IGF-I axis, whereas GHRH antagonists appear to reduce IGF-II production and interfere with the autocrine regulatory pathway. The antitumorigenic action of GHRH antagonists appears to be mediated by GHRH receptors found in OV-1063 tumors.
Asunto(s)
Antineoplásicos/uso terapéutico , Hormona Liberadora de Hormona del Crecimiento/análogos & derivados , Hormona Liberadora de Hormona del Crecimiento/antagonistas & inhibidores , Hormona Liberadora de Hormona del Crecimiento/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Sermorelina/análogos & derivados , Sermorelina/uso terapéutico , Somatostatina/análogos & derivados , Somatostatina/uso terapéutico , Animales , División Celular/efectos de los fármacos , Femenino , Hormona Liberadora de Hormona del Crecimiento/farmacología , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/genética , Factor II del Crecimiento Similar a la Insulina/análisis , Factor II del Crecimiento Similar a la Insulina/genética , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Neoplasias Ováricas/patología , ARN Mensajero/análisis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante Heterólogo , Células Tumorales CultivadasRESUMEN
The effects of transient ischemia on the metabolic responsiveness of a well-defined brain circuit were investigated with [14C]2-deoxyglucose autoradiography. Rats underwent 30 min of severe forebrain ischemia followed by postischemic recirculation periods of 1, 2, 3, 5, and 10 days. At these times, unilateral whisker stimulation was carried out, resulting in the metabolic activation of the whisker barrel circuit. An altered pattern of glucose utilization within both stimulated and nonstimulated circuit relay stations was observed at 1, 2, and 3 days following ischemia. At 1 day, stimulus-evoked increases in metabolic activity were severely depressed within both the ventrobasal thalamus and layer IV of the cortical barrel field region. Baseline metabolic rate within nonstimulated relay areas was also severely depressed at this time. At postischemic days 2 and 3, moderate levels of increased glucose utilization were apparent overlying cortical layer IV and the superficial half of layer VI, while layers I, II, III, and V appeared less responsive to metabolic activation. By day 5, whisker stimulation resulted in normal levels of increased glucose utilization within the activated ventrobasal thalamus and layer IV of the cortical barrel field region. Glucose utilization within nonactivated relay stations, depressed at earlier time periods, had also returned to control levels by day 5. At both 5 and 10 days, an altered laminar pattern of elevated glucose utilization was apparent within the activated barrel field region, with local CMRglu being depressed in layer V compared with control values. These results demonstrate that periods of transient ischemia produce both reversible and longer-lasting effects on the ability of the CNS to respond to peripheral activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Isquemia Encefálica/metabolismo , Corteza Somatosensorial/metabolismo , Animales , Autorradiografía , Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular , Desoxiglucosa/administración & dosificación , Metabolismo Energético , Glucosa/metabolismo , Masculino , Estimulación Física , Ratas , Ratas Endogámicas , Tálamo/metabolismo , Factores de TiempoRESUMEN
The effect of the serotonin (5-hydroxytryptamine, 5-HT) antagonist ketanserin on the remote hemodynamic consequences of thrombotic brain infarction was studied in rats. Treated rats received an injection of 1 mg/kg ketanserin 30 min before and 1 h following photochemically induced cortical infarction. Local CBF (LCBF) was assessed autoradiographically with [14C]iodoantipyrine 4 h following infarction, and chronic infarct size was documented at 5 days. Thrombotic infarction led to significant decreases in LCBF within noninfarcted cortical regions. For example, mean LCBF was decreased to 63, 55, and 65% of control (nontreated normal rats) in ipsilateral frontal, lateral, and auditory cortices, respectively. In rats treated with ketanserin, significant decreases in LCBF were not documented within remote cortical areas compared with controls. In contrast to these hemodynamic effects, morphological analysis of chronic infarct size demonstrated no differences in infarct volume between treated (27 +/- 3 mm3) and nontreated (27 +/- 6 mm3) rats. These data are consistent with the hypothesis that 5-HT is involved in the widespread hemodynamic consequences of experimentally induced thrombotic infarction. Remote hemodynamic consequences of acute infarction can be inhibited without altering final infarct size.
Asunto(s)
Infarto Cerebral/fisiopatología , Circulación Cerebrovascular/efectos de los fármacos , Enfermedad Coronaria/fisiopatología , Trombosis Coronaria/fisiopatología , Ketanserina/farmacología , Animales , Antipirina/análogos & derivados , Autorradiografía , Radioisótopos de Carbono , Masculino , Especificidad de Órganos , Ratas , Ratas Endogámicas , Valores de ReferenciaRESUMEN
Levels of energy metabolites were measured in forebrain regions in fasted rats subjected to 4-h recirculation after 1 h of either incomplete or complete ischemia. Both models of ischemia were produced by a procedure combining bilateral common carotid artery occlusion, systemic hypotension, and CSF pressure elevation; the degree of intracranial hypertension was varied to produce incomplete and complete ischemia. Levels of brain lactate at the end of ischemia ranged from 16 to 19 mmol/kg in incomplete ischemia and from 11 to 13 mmol/kg in complete ischemia. Energy metabolism recovered evenly in the neocortical and subcortical regions with recirculation after incomplete ischemia. The metabolic recovery in the cerebral cortex after complete ischemia was similar to that observed after incomplete ischemia; however, recovery in the subcortical regions after complete ischemia was less extensive, NADH fluorescence remained high, and there was a fall in total creatine. Intracellular pH in the dorsal thalamus was more alkalotic after complete than incomplete ischemia. Thus, in the absence of profound tissue lactic acidosis, residual CBF during prolonged ischemia helps postischemic restitution of brain energy metabolism in subcortical regions. The pattern of poor recovery in these regions after complete ischemia suggests inadequate reperfusion. The decreased total creatine and the severe tissue alkalosis may be biochemical markers of advanced tissue injury during reflow.
Asunto(s)
Acidosis/metabolismo , Isquemia Encefálica/metabolismo , Encéfalo/metabolismo , Metabolismo Energético , Lactatos/metabolismo , Alcalosis/metabolismo , Animales , Isquemia Encefálica/fisiopatología , Circulación Cerebrovascular , Fluorescencia , Glucosa/metabolismo , Concentración de Iones de Hidrógeno , Masculino , NAD , Ratas , Ratas EndogámicasRESUMEN
The primary objective of this study was to compare the histopathological consequences of complete versus incomplete ischemia under experimental conditions that limit lactate accumulation. Fasted rats underwent 1 h of either complete or incomplete ischemia by a procedure combining bilateral common carotid artery occlusion, halothane-induced systemic hypotension, and CSF pressure elevation. Histopathological outcome was evaluated 4 h later and was graded on a 4-point scale. Incomplete ischemia resulted in ischemic neuronal damage within selectively vulnerable brain regions. In contrast, complete ischemia, in addition to diffuse neuronal damage, resulted in focal sites of parenchymal necrosis with vascular stasis. Perfusion defects were detected by carbon black infusion within cortical and subcortical regions following only 25 min of complete, but not incomplete, ischemia. Ultrastructural abnormalities at the same duration of complete ischemia included a high frequency of endothelial microvilli and compressed lumina with severe perivascular astrocytic swelling. When recirculation was instituted for 1 h following 1 h of complete ischemia, regions of nonperfusion were detected autoradiographically. Thus, when the degree of lactic acidosis is controlled, prolonged periods of complete ischemia result in a more severe pathological outcome compared to incomplete ischemia. Focally impaired postischemic cerebral perfusion appears to be an important factor in infarct formation under the present experimental conditions.
Asunto(s)
Isquemia Encefálica/patología , Encéfalo/patología , Circulación Cerebrovascular , Animales , Autorradiografía , Encéfalo/ultraestructura , Isquemia Encefálica/fisiopatología , Arterias Carótidas/fisiología , Constricción , Hemodinámica , Masculino , Microscopía Electrónica , Ratas , Ratas EndogámicasRESUMEN
Studies were directed toward defining relationships between brain ion transport, glycolysis, and oxidative phosphorylation. This was done by examining the relative sensitivity to hypoxemia and to iodoacetate (IAA)-induced inhibition of glycolysis in rats anesthetized with pentobarbital. Both insults had minimal effects on K+o baseline. In response to neuronal activation, IAA increased the time required for K+o clearance from maximal values to half-recovery of baseline. Hypoxemia slowed the later phase of K+o clearance, when K+o was approaching "resting" levels. Hypoxemia produced greater declines in high-energy intermediates than did IAA, which indicated that the IAA effect was not due to a greater overall insult to metabolism and suggested a direct link between ATP produced by glycolysis and ion transport activity. These data demonstrate that K+o clearance requires energy from glycolysis and oxidative phosphorylation for different phases of the recovery process and that inhibition specific to glycolysis or oxidative phosphorylation may be temporally resolved within a single stimulus.
Asunto(s)
Encéfalo/metabolismo , Glucólisis , Fosforilación Oxidativa , Potasio/farmacocinética , Animales , Metabolismo Energético , Yodoacetatos/metabolismo , Ácido Yodoacético , Masculino , Ratas , Ratas EndogámicasRESUMEN
Alterations in local CBF (LCBF) were assessed autoradiographically in the rat at several time points following photochemically induced cortical infarction. Cortical infarction of consistent size and location was produced by irradiating the brain with green light through the intact skull for 20 min following the systemic injection of rose bengal. A consistent pattern of altered LCBF was recorded in both ipsilateral and contralateral brain regions over the course of the study. At 30 min, a severely ischemic zone surrounded by regions of cortical hyperemia was apparent. LCBF was also depressed relative to control values in ipsilateral cortical regions remote from the irradiated area, while contralateral cortical structures were mildly hyperemic. By 4 h, the zone of severe ischemia had enlarged and its margins were no longer hyperemic. Ipsilateral cortical and some subcortical structures demonstrated significantly depressed levels of LCBF. At 5 days, LCBF throughout both ipsilateral and contralateral cortices was depressed compared with control values. By 15 days, LCBF had returned to control levels in most brain structures shown histopathologically not to be irreversibly damaged. The temporal sequence and magnitude of these hemodynamic alterations are consistent with findings in clinical studies in which repeated measurements of CBF have been carried out in patients with acute stroke. The ability to produce a cortical infarct that results in a consistent pattern of altered CBF should facilitate the investigation of stroke mechanisms responsible for these hemodynamic abnormalities.
Asunto(s)
Corteza Cerebral/patología , Infarto Cerebral/fisiopatología , Circulación Cerebrovascular , Hemodinámica , Animales , Autorradiografía , Infarto Cerebral/etiología , Infarto Cerebral/patología , Embolia y Trombosis Intracraneal/etiología , Embolia y Trombosis Intracraneal/fisiopatología , Luz/efectos adversos , Masculino , Fotoquímica , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
Local CMRglu (LCMRglu) values were measured by [14C]2-deoxyglucose autoradiography in the rat at 4 h and 5 days following photochemically induced cortical infarction, and these data were compared with neuropathological findings in adjacent serial sections. At both time periods, LCMRglu was markedly reduced within the lesion center, and irregular regions of moderate-to-marked glucose hypermetabolism were noted within the marginal zone of the developing infarct. At 4 h, the hypermetabolic zones were shown by pathological examination to be characterized by normal-sized, moderately hyperchromatic neurons scattered among occasional dark, shrunken neurons within preserved neuropil. In contrast, the hypermetabolic zones at 5 days coincided with foci of intense macrophage infiltration, with dissolution of the neuropil. Significant decreases in glucose utilization were also demonstrated at 4 h within brain structures remote from the site of focal injury. These structures included the lateral and auditory cortices ipsilaterally, the striatum and thalamus ipsilaterally, and the hippocampus bilaterally. In addition to these remote metabolic effects, depressed metabolism occurred within the homologous cortical region contralateral to the site of infarction. By 5 days, glucose utilization was severely depressed in all ipsilateral cortical regions but not within any contralateral cortical region. Analysis of these data suggests that more than one mechanism is responsible for the metabolic alterations occurring within brain regions remote from the site of irreversible damage. Results are discussed in light of the hemodynamic alterations occurring in this stroke model, which are presented in the accompanying report.
Asunto(s)
Corteza Cerebral/metabolismo , Infarto Cerebral/metabolismo , Glucosa/metabolismo , Animales , Autorradiografía , Corteza Cerebral/patología , Infarto Cerebral/etiología , Infarto Cerebral/patología , Desoxiglucosa , Luz/efectos adversos , Masculino , Fotoquímica , Ratas , Ratas EndogámicasRESUMEN
Using autoradiographic image-averaging strategies, we studied the relationship between local glucose utilization (LCMRglc) and blood flow (LCBF) in a highly reproducible model of transient (2-hour) middle cerebral artery occlusion (MCAO) produced in Sprague-Dawley rats by insertion of an intraluminal suture coated with poly-L-lysine. Neurobehavioral examination at 60 minutes after occlusion substantiated a high-grade deficit in all animals. In two subgroups, LCBF was measured with 14C-iodoantipyrine at either 1.5 hours of MCAO, or at 1 hour of recirculation after suture removal. In two other matched subgroups, LCMRglc was measured with 14C-2-deoxyglucose at 1.5 to 2.25 hours of MCAO, and at 0.75 to 1.5 hours of recirculation after 2 hours of MCAO. Average image data sets were generated for LCBF, LCMRglc, and the LCMRglc/LCBF ratio for each study time. Middle cerebral artery occlusion for 2 hours induced graded LCBF decrements affecting ipsilateral cortical and basal ganglionic regions. After 1 hour of recirculation, LCBF in previously ischemic neocortical regions increased by 40% to 200% above ischemic levels, but remained depressed, on average, at about 40% of control. By contrast, frank hyperemia was noted in the previously ischemic caudoputamen. Mean cortical LCBF values during MCAO correlated highly with their respective LCBF values after 1 hour of recirculation (R = 0.93), suggesting that post-ischemic LCBF recovery is related to the depth of ischemia. Despite focal ischemia, LCMRglc during approximately 2 hours of MCAO was preserved, on average, at near-normal levels; but following approximately 1 h of recirculation, LCMRglc became markedly depressed (on average, 55% of control in previously densely ischemic cortical regions). Regression analysis indicated that this depressed glucose utilization was determined largely by the intensity of antecedent ischemia. By pixel analysis, the ischemic core (defined as LCBF 0% to 20% of control) comprised 33% of the ischemic hemisphere, and the penumbra (LCBF 20% to 40%) accounted for 26%. The penumbra was concentrated at the coronal poles of the ischemic lesion and formed a thin shell around the central ischemic core. During 2 hours of MCAO, the LCMRglc/LCBF ratio within the ischemic penumbra was increased four-fold above normal (average, 179 umol/100 mL). In marked contrast, after approximately 1 h recirculation, this uncoupling had almost completely subsided. The companion study (Zhao et al., 1997) further analyzes these findings in relation to patterns of infarctive histopathology.