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Repetitive apnea is associated with a significant increase in extracellular dopamine, generation of free radicals as determined by o-tyrosine formation and increase in Fluoro-Jade staining of degenerating neurons. This increase in extracellular dopamine and of hydroxyl radicals in striatum of newborn brain is likely to be at least partly responsible for the neuronal injury and neurological side effects of repetitive apnea.

It can be seen from this brief review that the short period of time since the publication of the human genome sequences has been an era of considerable discovery in the human respirome. This era has revealed new molecules involved in intra-cellular oxygen binding and as components of ETC complexes, while new pathways have emerged in the process of apoptosis. In terms of the involvement of the human respirome in cancer susceptibility and responses, important new discoveries have also been reported. The impact of some of these discoveries on our understanding of the oxygen cascade will be significant, requiring major adjustments in the models that have been developed in the past three decades. The impact of the revelations regarding association of mutations in human respirome components with particular cancers is of even wider significance. It is perhaps appropriate that these associations will force a reconsideration of the role of cellular respiration in cancer initiation and proliferation.

Theoretical simulation of tissue oxygenation is a robust method that can be used to quantify the tissue oxygenation for a variety of applications. However, it is necessary that the relevant input parameters are used for the model describing the tumour microenvironment. The results of the simulations presented in this article suggest that the accuracy of the simulations depends very much on the method of calculation of the effects of the temporal change of the hypoxic pattern due to the opening and the closure of blood vessels. Thus, the use of average oxygenations might lead to dangerous overestimations of the treatment response. This indicates that care should be taken when incorporating hypoxia information into the biological modelling of tumour response.

Our simulations suggested that measurements performed in a limited number of points in the tumour can be representative for the situation in the whole tumour. It has further been shown that the polarographic electrode cannot be used to measure small regions of hypoxia. In fact it has been suggested that the most important factor that determines the efficiency of the polarographic electrode is the spatial distribution of the hypoxic cells and not their type, and therefore the polarographic electrode cannot be used to make the distinction between acute and chronic hypoxia. The simulations have also shown that it is reasonable to assume that the electrode measurement can be correlated to the situation in the whole tissue, even though the correlation is only qualitative. And because the electrode measurements are greatly influenced by the averaging process, the quantitative use of the electrode measurements may lead to erroneous results, especially for modelling the treatment response.