dc.contributor.advisor |
Davis, Mike |
en |
dc.contributor.advisor |
Dawson, Noel |
en |
dc.contributor.author |
Gorman, Desmond Francis |
en |
dc.date.accessioned |
2009-11-19T03:36:58Z |
en |
dc.date.available |
2009-11-19T03:36:58Z |
en |
dc.date.issued |
2006 |
en |
dc.identifier |
W4 G671 2006 |
en |
dc.identifier.citation |
Thesis (MD)--University of Auckland, 2006. |
en |
dc.identifier.uri |
http://hdl.handle.net/2292/5543 |
en |
dc.description |
Full text is available to authenticated members of The University of Auckland only. |
en |
dc.description.abstract |
Carbon monoxide (CO) is probably a neural messenger and yet inspiring CO can be lethal or disabling. The best treatment for a survivor of a CO exposure is controversial for several reasons. First, meritorious clinical studies are difficult. The prospective study conducted at the Royal Adelaide Hospital and reported in this thesis was typically troubled, but did show a benefit for hyperbaric over normobaric oxygen in preventing sequelae (NNT = 2.04 to 3.7). Second, many poisonings are deliberate. Third, the toxicology of CO is not agreed, such that proposed treatments cannot be easily rationalised.
A better understanding of the acute toxicology of CO is a prerequisite to resolving how best to treat a poisoned person. A series of in vivo experiments were consequently conducted on rabbits and sheep. Examination of the brains of sheep that were killed days after being anaesthetised with CO showed little injury. The cortex was unharmed, whereas scattered white matter infarcts and an associated gliosis and axonal dysfunction were usual. Some mechanisms were found that could explain this cortical preservation.
First, hypoxaemia induced an increase in heart rate, cardiac output and brain blood flow (BBF). This response was strongly correlated with the oxyhaemoglobin (O2Hb) level and near-perfectly maintained O2 delivery to the brain. Until the limits of this response were exceeded (O2Hb < 20%), brain O2 uptake was adequate for normal function and there was no evidence of brain hypoxia. Despite this normoxia, a cortical somatosensory evoked response was suppressed and sheep were narcotised by CO inhalation. Exhaustion of this circulatory response resulted in suddenly lethal hypoxia.
Second, blood O2 carriage was enhanced by an increase in circulating red blood cells. This might be species specific.
Third, both neuronal haeme oxygenase and nitric oxide synthetase were induced. This was apparently protective for the brain cortex as blockade of these enzymes caused cortical dysfunction and infarction. The consequent hypothesis is that this protection occurs by way of a blood steal from white matter to cortex and is mediated by CO and nitric oxide.
Fourth, in experiments that are not reported here, neuronal synaptic function appears to be unaffected by CO per se.
Fifth, sheep exposed to CO showed a sympathetic response that would preferentially perfuse the brain and heart. This was accompanied by induction of protein-kinase C in the amygdala, which is the most well recognised regulatory brain centre for stress responses. This and the correlation between the BBF and O2Hb levels suggest that the response to CO is regulated.
Given the quality of the brain protection, in order of decreasing likelihood, it is hypothesized that persistent health problems in people who have been poisoned by CO are due to: a pre-morbid mental health problem; a psychological reaction to the stressor of the exposure and related events; a delayed vascular and immunological brain injury; an injury caused by other concurrent poisons; and, a hypoxic brain injury suffered because of apnoea, asphyxia and/or aspiration, or as a consequence of a failure of circulatory compensation to hypoxaemia.
The cortical protection against CO-induced hypoxaemia warrants further study. Identifying the relevant mechanisms might facilitate the development of treatments for CO poisoned people. Extrapolation of novel therapies to other situations of hypoxaemia is also possible. |
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dc.publisher |
ResearchSpace@Auckland |
en |
dc.relation.ispartof |
PhD Thesis - University of Auckland |
en |
dc.relation.isreferencedby |
UoA99170983014002091 |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
en |
dc.rights |
Restricted Item. Available to authenticated members of The University of Auckland. |
en |
dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
en |
dc.title |
Preservation of the brain cortex during and after carbon monoxide-induced hypoxaemia |
en |
dc.type |
Thesis |
en |
thesis.degree.discipline |
Medicine |
en |
thesis.degree.grantor |
The University of Auckland |
en |
thesis.degree.level |
Doctoral |
en |
thesis.degree.name |
MD |
en |
dc.subject.marsden |
Fields of Research::320000 Medical and Health Sciences::320100 Medicine-General |
en |
dc.rights.holder |
Copyright: the author |
en |
pubs.local.anzsrc |
110000 Medical and Health Sciences |
en |
dc.identifier.wikidata |
Q112868135 |
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