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Biomedical subjects

Des Gorman

Publications and source records attributed to Des Gorman.

8 recordsLinked to original sources
PubMed2005

Early evidence of a regulated response to hypoxaemia in sheep that preserves the brain cortex.

Hypoxaemia consequent to inspired carbon monoxide (CO), and to other causes, often does not injure the brain cortex. At least five types of brain and heart protective cardiovascular response to hypoxaemia have been reported. The underlying mechanism is unknown. The present study was designed to test the hypothesis that the reaction to inspired CO involves the amygdala as this structure is thought to be central to stress responsivity; involvement would support the additional hypothesis that the somatic response to CO-hypoxaemia is regulated. Eighteen ewes were randomly allocated to control and two CO groups. The CO groups were exposed to 1% CO for 120 min and killed either 5 or 15 days later. This exposure caused isolated white matter brain injury and a transient increase in protein-kinase C (gamma) activity in the pyramidal neurons in the nuclei of the central and basal-lateral amygdala and in the neurons of the audio-cortex (p < 0.05). This was associated with evidence of a sympathetic response. It would seem reasonable to hypothesise both that the amygdala is important in the processes by which the hypoxaemic effects of CO on the brain are prevented, delayed and/or mitigated and that these processes are regulated.

Amygdala↗
PubMed2005

Blockade of haem oxygenase and nitric oxide synthetase causes cortical dysfunction in sheep exposed to carbon monoxide.

Twenty adult ewes underwent common surgery and following recovery were exposed to 1% carbon monoxide (CO) for 2 h. Ten of these sheep were randomly selected for treatment with haem oxygenase (HO) and nitric oxide synthetase (NOS) blockers. All sheep were killed 5 days later. The CO exposure was narcotic and EEG frequency was suppressed. The EEG recovery was rapid in the control sheep and both slow and incomplete in the treated sheep. This difference was statistically significant (P<0.05). For the first time in our CO studies in sheep, one showed multiple cortical infarcts. This sheep was blocked for HO and NOS function. No significant differences were seen in peri-ventricular white matter infarction distribution and frequency. We have previously shown brain protection against CO- and inert diluent-hypoxemia by way of an increase in brain blood flow (BBF) that maintains adequate brain O2 uptake, and by an increase in circulating red blood cells. From this study, we propose that the induction of neuronal and glial HO and NOS in sheep exposed to CO is protective, especially for the cortex. We intend to study this further by both selective and collective enzyme blockade and by measuring regional BBF changes.

Animals↗
PubMed2003

The clinical toxicology of carbon monoxide.

Carbon monoxide (CO) is a dangerous exogenous poison and an essential endogenous neurotransmitter. This gas when inhaled has an anaesthetic effect, which is poorly understood, but which may be fatal if compensatory mechanisms are exhausted, if cardiac oxygen (O(2)) needs exceed myocardial oxygenation and/or if apnoea or asphyxia onsets. Although there is considerable evidence that hypoxia occurs late in CO poisoning, both the treatment of acutely poisoned people and environmental exposure limits are largely based on a hypoxic theory of toxicity. The significance of recent demonstrations of increased endogenous CO and NO production in neurons of animals exposed to exogenous CO, and of a related sequestration of leucocytes along the endothelium and subsequent diapedesis is also not fully understood, but may in part explain both acute and delayed deleterious effects of a CO exposure. Delayed brain injuries due to a CO exposure may be preventable by hyperbaric O(2). However, the ideal dose of O(2) in this context, if any, is unknown and other potential treatments need to be tested.

Animals↗
PubMed2003

A lignocaine infusion worsens the leukoencephalopathy due to a carbon monoxide exposure in sheep.

Poisoning by carbon monoxide (CO) is common and conventional treatment of affected people is frequently unsuccessful. Lignocaine was identified as a potential therapy in this context because of the benefit shown for it in other brain injuries for which the received toxic mechanisms are similar. Twelve Romney ewes were exposed to 1% CO for 120 min were then infused intravenously with either lignocaine (N=6) or saline for 72 h, and were killed 5 days after the exposure for histological and immunohistochemical examination. This dose of CO was narcotic and caused white matter brain infarcts, with associated glial cell activation, axonal dysfunction and induction of both neuronal and glial haeme oxygenase and nitric oxide synthetase. The frequency of the white matter infarcts was significantly greater in the lignocaine-treated group. The mechanism of this adverse interaction is neither established here nor is it deducible from other published data; alternative antidotes to CO clearly need to be tested.

Animals↗
PubMed2002

A narcotic dose of carbon monoxide induces neuronal haeme oxygenase and nitric oxide synthetase in sheep.

Twelve Romney ewes were exposed to either 1% carbon monoxide (CO) in air (n=6) or room air alone for 120 min and were killed 15 days later for histological and immunohistochemical examination. This dose of CO was narcotic and induced both haeme oxygenase and nitric oxide synthetase in brain neurons, but not in endothelial cells. The mechanism of the induction is not established here, but cellular theories of CO toxicity will need to be re-examined given these results.

Animals↗
PubMed2002

The pathophysiology of cerebral arterial gas embolism.

Bubbles are introduced to the arterial circulation in many patients undergoing cardiac surgical procedures, and some of these distribute to the cerebral vessels. Larger bubbles may arrest in cerebral arterioles, causing ischemia and neuronal injury in the downstream territory. Smaller bubbles may redistribute through the cerebral circulation, but this is not a benign event. Their passage may cause transient ischemia and cause damage to endothelium. Margination and activation of leukocytes follows, and may cause a secondary ischemia. Although the potential of large bubbles to cause cerebral injury is not disputed, there is controversy over the significance of exposure to small bubbles in cardiac surgery. It is known that postsurgical neuropsychological deficits do correlate positively with numbers of emboli to which patients are exposed, but to date, the technology to distinguish between gaseous and particulate emboli or to size emboli accurately is not readily available. Until this technology becomes available and is applied in large studies designed to determine the importance of small bubbles, it seems prudent to take all practical steps to prevent introduction of arterial bubbles in cardiac surgery.

Cerebral Arteries↗