Comparison of the Neuroapoptotic Properties of Equipotent Anesthetic Concentrations of Desflurane, Isoflurane, or Sevoflurane in Neonatal Mice
ABSTRACT Volatile anesthetics facilitate surgical procedures and imaging studies in millions of children every year. Neuronal cell death after prolonged exposure to isoflurane in developing animals has raised serious concerns regarding its safe use in children. Although sevoflurane and desflurane are becoming more popular for pediatric anesthesia, their cytotoxic effects have not been compared with those of isoflurane. Accordingly, using newborn mice, the current study established the respective potencies of desflurane, isoflurane, and sevoflurane and then compared equipotent doses of these anesthetics regarding their effects on cortical neuroapoptosis.
Minimum alveolar concentrations were determined in littermates (aged 7-8 days, n = 42) using tail-clamp stimulation in a bracketing study design. By using equipotent doses of approximately 0.6 minimum alveolar concentration, another group of littermates was randomly assigned to receive desflurane, isoflurane, or sevoflurane or to fast in room air for 6 h. After exposure, animals (n = 47) were euthanized, neocortical apoptotic neuronal cell death was quantified, and caspase 3 activity was compared between the four groups.
The minimum alveolar concentration was determined to be 12.2% for desflurane, 2.7% for isoflurane, and 5.4% for sevoflurane. After a 6-h exposure to approximately 0.6 minimum alveolar concentration of desflurane, isoflurane, or sevoflurane, neuronal cell death and apoptotic activity were significantly increased, irrespective of the specific anesthetic used.
In neonatal mice, equipotent doses of the three commonly used inhaled anesthetics demonstrated similar neurotoxic profiles, suggesting that developmental neurotoxicity is a common feature of all three drugs and cannot be avoided by switching to newer agents.
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ABSTRACT: Purpose. Sevoflurane, one of the most used general anesthetics, is widely used in clinical practice all over the world. Previous studies indicated that sevoflurane could induce neuron apoptosis and neural deficit causing query in the safety of anesthesia using sevoflurane. The present study was designed to investigate the effects of sevoflurane on electrophysiology in Drosophila pupa whose excitatory neurotransmitter is acetylcholine early after sevoflurane exposure using whole brain recording technique. Methods. Wide types of Drosophila (canton-s flies) were allocated to control and sevoflurane groups randomly. Sevoflurane groups (1% sevoflurane; 2% sevoflurane; 3% sevoflurane) were exposed to sevoflurane and the exposure lasted 5 hours, respectively. All flies were subjected to electrophysiology experiment using patch clamp 24 hours after exposure. Results. The results showed that, 24 hours after sevoflurane exposure, frequency but not the amplitude of miniature excitatory postsynaptic currents (mEPSCs) was significantly reduced . Furthermore, we explored the underlying mechanism and found that calcium currents density, which partially regulated the frequency of mEPSCs, was significantly reduced after sevoflurane exposure . Conclusions. All these suggested that sevoflurane could alter the mEPSCs that are related to synaptic plasticity partially through modulating calcium channel early after sevoflurane exposure.01/2015; 2015:1-7. DOI:10.1155/2015/485709
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ABSTRACT: General anesthesia in patients with or at risk for neuronal injury remains challenging due to the controversial influence of volatile anesthetics on neuronal damage. We hypothesized that isoflurane, sevoflurane, and desflurane would exert variable degrees of neurotoxicity in vitro and in vivo via activation of the p75 neurotrophin receptor (p75).Anesthesia and analgesia 12/2014; 119(6):1429. DOI:10.1213/ANE.0000000000000488 · 3.42 Impact Factor
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ABSTRACT: Background. Transplants cause ischemia-reperfusion (IR) injury that can affect distant organs. Liver is particularly sensitive to IR injury. The present randomized experimental study was designed to investigate a possible protective effect of sevoflurane against liver inflammatory response to lung IR in a lung upper lobe left autotransplant model. Methods. Two groups (sevoflurane and control) of eight swines each were submitted to upper lobe left lung autotransplant. Hypnotic maintenance was performed with sevoflurane 3% or propofol 8 to 10 mg/kg per hr until pneumonectomy was done; then propofol was used for all animals. Blood and liver samples were taken in four different moments: prepneumonectomy, prereperfusion, 10 min postreperfusion and 30 min postreperfusion to measure levels of interleukin (IL)-1 beta, IL-10, tumor necrosis factor (TNF)-alpha, monocyte chemotactic protein (MCP)-1, nuclear factor (NF)-kappa B, C-reactive protein, ferritin and caspase 3. Non-parametric test was used to find statistical meaning. Results. Lung IR markedly increased the expression of TNF-alpha, IL-1 beta, MCP-1, NF-kappa B and caspase activity in control livers compared with basal levels, whereas liver IL-10 expression decreased 10 and 30 min post-reperfusion. Sevoflurane significantly decreased TNF-alpha, IL-1 beta, MCP-1, NF-kappa B liver expression and caspase 3 activity. Sevoflurane also reverted the lung IR-induced decrease in IL-10 expression. Conclusions. The present results indicate that lung IR caused hepatic injury. Sevoflurane attenuated liver injury in a model of upper lobe left lung autotransplant in pigs.Transplantation 09/2014; DOI:10.1097/TP.0000000000000408 · 3.78 Impact Factor