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Advances in anesthetic management of pediatric patients now afford a safe clinical environment for the repair of complex congenital defects. Parallel evolution of technology in surgical approaches, constantly challenge the limits of physiology and demand the expansion of clinical practice to uncharted territories. This is clearly exemplified in the growing concern of the long-term safety of anesthetics agents in pediatric patients with multiple or prolonged exposures to certain groups of anesthetics. Over the past decade, cumulative experimental data in animals and clinical studies in humans suggest that anesthesia during critical stages of brain development can result in accelerated neurodegeneration with potential detrimental effects. The effects of pharmacologic agents designed to antagonize the normal neurotransmission have been implicated directly in cognitive deficits related to learning skills and neurodevelopment. Specifically, N-methyl-D-aspartate (NMDA) receptor antagonist have been demonstrated in animal and in vitro models to accelerate mechanisms of apoptosis by allowing the cell to prematurely engage in the normal cell cycle, resulting in apoptosis and cell death. These studies have identified a dose dependent aberrant induction of cell cycle proteins Cyclin-D1, Cyclin-dependent Kinase 4, E2F1 and Bim in primary neurons co-incubated with the NMDA receptor antagonist Ketamine. Expression of these proteins correlated with known markers of apoptosis (caspase-3 expression) both in vivo and in vitro. Although there may be numerous mechanisms by which NMDA receptor antagonism promote early apoptosis in cultured cells, this data supports the theory that cell cycle activation may play an important role in the potential cognitive effect suggested by clinical studies using Ketamine as primary anesthetic agent. This study did not evaluate potential cognitive effects in animals receiving Ketamime and is limited to findings in cell culture and fixed animal brains.

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2011-11-14   |   680 visitas   |   Evalua este artículo 0 valoraciones

Vol. 39 Núm.4. Octubre-Diciembre 2011 Pags. 471-475 Rev col anest 2011; 39(4)