Use of xenon as neuroprotectant in a neonatal subject

Abstract

The present invention relates to the use of xenon in the preparation of a medicament for preventing and / or alleviating one or more anesthetic-induced neurological deficits in a neonatal subject. The present invention further relates to combinations of xenon and sevoflurane, and use thereof as preconditioning agents for administration prior to hypoxic-ischaemic injury.

Description

[0001]The present invention relates to the field of anesthetics. More specifically, the invention relates to anesthetic agents suitable for use in newborn and / or fetal subjects.BACKGROUND TO THE INVENTION[0002]Xenon's anesthetic properties have been known to the medical profession for over 50 years (Cullen and Gross, 1951). However, despite some impressive displays of clinical efficacy in patients (Luttropp et al., 1994; Lynch et al., 2000), everyday use of xenon anesthesia has failed to materialize. This is largely associated with the significant cost involved in production of xenon through fractional distillation of liquid air, and hence the relatively small percentage of the total refined quantity of xenon available for anesthesia (Hanne Marx et al., 2001). Consequently, use of xenon is likely to be restricted to special areas where there is an appreciable cost-benefit advantage. One such area may be neonatal anesthesia, where xenon may lack harmful side effects seen with other c...

AI Technical Summary

Benefits of technology

[0017]An in vivo rat model of anesthesia was used in conjunction with both histology and immunohistochemistry to identify and quantify apoptosis induced by various combinations of anesthetic agents. Unlike isoflurane, xenon did not induce any apoptotic neurodegeneration above the baseline observed in controls. Additionally, it was found that whilst nitrous oxide enhances isoflurane-induced apoptosis, xenon reduces the degree of injury.

[0179]Yet another aspect of the invention relates to the use of xenon and isoflurane in the preparation of a medicament for use as a preconditioning agent for protecting against hypoxic injury.

Problems solved by technology

However, despite some impressive displays of clinical efficacy in patients (Luttropp et al., 1994; Lynch et al., 2000), everyday use of xenon anesthesia has failed to materialize.

This is largely associated with the significant cost involved in production of xenon through fractional distillation of liquid air, and hence the relatively small percentage of the total refined quantity of xenon available for anesthesia (Hanne Marx et al., 2001).

Consequently, use of xenon is likely to be restricted to special areas where there is an appreciable cost-benefit advantage.

Later work done by Jevtovic-Todorovic et al. showed that neonatal rats are vulnerable to harmful side effects of anesthesia during the synaptogenic period.

They demonstrated up to a 68-fold increase in the number of degenerating neurones above baseline in areas such as the laterodorsal and anteroventral thalamic nuclei (and to some extent layer II of the parietal cortex) after exposure to anesthetic agents (Jevtovic-Todorovic et al., 2003), which resulted in a functional neurological deficit in behaviour tests later in life.

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