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Arcusa Mon, Maria Jesús
Gallego García, Juan (dir.); Errando Oyonarte, Carlos Luis (dir.) Universitat de València - FISIOLOGIA |
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Aquest document és un/a tesi, creat/da en: 2005 | |
There are published numerous studies on the ketamine administered by experimentation subarachnoid animal route and in humans, nevertheless the data on the neurotoxicity that produces are controverted.
The work hypothesis is based on to demonstrate that to the isomer levogiro of the ketamine (S(+)K) and the racemic mixture of the ketamine without preservative (RSK) administered by subarachnoid route in rabbits produce blockade both sensitive and motor and have little toxicity neurological.
60 white rabbits were used of race New Zealand male of between 2-3 kg of weight. The study was randomized and double blind person. The 60 rabbits distributed themselves in 6 groups of 10 rabbits, according to the drug administered by subarachnoid route: S+K: 2mg/Kg. RSK: 4mg/Kg. Lidocaine(L)2%: 1'5mg/Kg. L5%: 4mg/Kg. Like negative control physiological serum 0'9%(SF): 0'2 mililiter and positive contr...
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There are published numerous studies on the ketamine administered by experimentation subarachnoid animal route and in humans, nevertheless the data on the neurotoxicity that produces are controverted.
The work hypothesis is based on to demonstrate that to the isomer levogiro of the ketamine (S(+)K) and the racemic mixture of the ketamine without preservative (RSK) administered by subarachnoid route in rabbits produce blockade both sensitive and motor and have little toxicity neurological.
60 white rabbits were used of race New Zealand male of between 2-3 kg of weight. The study was randomized and double blind person. The 60 rabbits distributed themselves in 6 groups of 10 rabbits, according to the drug administered by subarachnoid route: S+K: 2mg/Kg. RSK: 4mg/Kg. Lidocaine(L)2%: 1'5mg/Kg. L5%: 4mg/Kg. Like negative control physiological serum 0'9%(SF): 0'2 mililiter and positive control: Phenol 8%:6 mg/Kg, administered a volume of 0'2 mililiter. After the subarachnoid injection of the drug it was come to motor and sensitive clinical valuation: immediate, up to the 5 minutes, 30 and until the disappearance of the effects and up to 48 hours. The adjudged valuation to each one of the three ítems was: 0 = normal answer, 1 = answer diminished as opposed to normality and 2 = absent answer. To the 7 days rabbits were sacrificed and immediately it was come to the dissection and extraction of a block of lumbar vertebrae and first sacred and another block a thoracic level. They were included in formaldehyde to 10% during 7 days, later the spinal marrow was extracted, cuts were made up to 1 micron, they were used the hematoxylin-eosin´s stain to value the structures cellular and luxol phase blue for the cases of mielina. White substance components suchs as cellular components, astrocytes, oligodendroglia and myelin sheath were evaluated. Grey substance components such as cellular components, oligodendroglia, astroglia and the neurons were as well evaluated. A valuation from 0 occurred to 3, value 0 corresponded to normality, value 1 to slight injuries, value 2 to moderate injuries and value 3 to serious injuries.
The statistical analysis of the data was made with computer science program SPSS version 9.0, by the Kruskall-wallis test and the Tau-b of Kendall test. The results were considered significant when p<0'05.
Since the evaluation clinic significant differences between group SF with the others were observed of groups. In the group of rabbits to which it was injected SF were not observed alterations, in the rest of groups was sawn paralysis of the legs back. In the evaluation made to the 30 minutes there were differences significant between groups SF, S+K and RSK in which had disappeared as well the blockade motor as the blockade sensitive, when they were compared with groups L5% and F8% in which a more intense blockade persisted . In evaluation carried out 48 hours after the injection, showed paralysis irreversible only in the animals corresponding to group F8%.
All the histologys structures studied of the samples of the rabbits pertaining to groups S+K, RSK, L2% and L5% showed significant differences when they were compared with groups negative and positive control. F8% produced injuries from moderate degree to severe degree, L5% produced injuries both intense and moderate degree. The S+K, RSK and L2% were the less damaging drugs.
Given the little toxicity of the S+K and the RSK, they could be used in human beings for regional anesthesia and for the treatment of chronic pain from any resistant etiology to the therapy with morphine, such as in guidelines well combined.RESUMEN
Hay publicados numerosos estudios sobre la ketamina administrada por vía subaracnoidea en animales de experimentación y en humanos, sin embargo los datos sobre la neurotoxicidad que produce son controvertidos.
La hipótesis de trabajo se basa en demostrar que el isómero levógiro de la ketamina (S(+)K) y la mezcla racémica de la ketamina sin conservantes (RSK) administradas por vía subaracnoidea en conejos producen bloqueo sensitivo y motor y tienen escasa toxicidad neurológica.
Se emplearon 60 conejos blancos de la raza New Zealand machos de entre 2-3 Kg de peso. El estudio fue aleatorizado y doble ciego. Los 60 conejos se distribuyeron en 6 grupos de 10 conejos, según el fármaco administrado por vía subaracnoidea: S+K: 2mg/Kg. RSK: 4mg/Kg. Lidocaína(L)2%: 15mg/Kg. L5%: 4mg/Kg. Como control negativo suero fisiológico 09%(SF): 02 ml y control positivo: Fenol 8%:6 mg/Kg, Se administró un volumen de 02 ml. Tras la inyección subaracnoidea del fármaco se procedió a la valoración clínica motora y sensitiva: inmediata, a los 5 minutos, a los 30 y hasta la desaparición de los efectos y a las 48 horas. La valoración adjudicada a cada uno de los tres ítems fue: 0=respuesta normal, 1=respuesta disminuida frente a la normalidad y 2=respuesta ausente. A los 7 días los conejos eran sacrificados e inmediatamente se procedía a la disección y extracción de un bloque de vértebras lumbares y primeras sacras y otro bloque a nivel torácico. Se incluían en formaldehído al 10% durante 7 días, posteriormente se extraía la médula espinal, se realizaban cortes de 1 micra, se emplearon la tinción hematoxilina-eosina para valorar las estructuras celulares y luxol fase blue para las vainas de mielina. En la sustancia blanca se evaluaron sus componentes celulares, astrocitos, oligodendroglía y vainas de mielina. En la sustancia gris se evaluaron sus componentes celulares, oligodendroglía, astroglía y las neuronas. Se dio una valoración de 0 a 3, el valor 0 correspondía a la normalidad, el valor 1 a lesiones leves, el valor 2 a lesiones moderadas y el valor 3 a lesiones graves.
El análisis estadístico de los datos se realizó con el programa informático SPSS versión 9.0, mediante el test de Kruskall-wallis y la prueba de la Tau-b de Kendall. Los resultados fueron considerados significativos cuando p<005.
Desde el punto de vista de la evaluación clínica se observaron diferencias significativas entre el grupo SF con el resto de grupos. En el grupo de conejos a los que se inyectó SF no se observaron alteraciones, en el resto de grupos se objetivó parálisis de las patas traseras. En la evaluación realizada a los 30 minutos hubo diferencias significativas entre los grupos SF, S+K y RSK en los que había desaparecido tanto el bloqueo motor como el bloqueo sensitivo, cuando se comparaban con los grupos L5% y F8% en los que persistía un bloqueo algo más intenso. En la evaluación llevada a cabo 48 horas después de la inyección, mostró parálisis irreversible sólo en los animales correspondientes al grupo F8%.
Todas las estructuras histológicas estudiadas de las muestras de los conejos pertenecientes a los grupos S+K, RSK, L2% y L5% mostraron diferencias significativas cuando fueron comparadas con los grupos control negativo y positivo. El F8% produjo lesiones de grado moderado a severo, la L5% lesiones de grado intenso y moderado. El S+K, RSK y L2% son los fármacos que menos daños produjeron.
Dada la escasa toxicidad del S+K Y de la RSK, podrían ser utilizados en seres humanos para anestesia regional y para el tratamiento del dolor crónico de cualquier etiología resistente a la terapia con morfina, o bien en pautas combinadas.
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