UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Mechanisms of cerebral injury and strategies for neuroprotection following deep hypothermic circulatory arrest in the neonatal piglet

Langley, StephenMark; (1999) Mechanisms of cerebral injury and strategies for neuroprotection following deep hypothermic circulatory arrest in the neonatal piglet. Doctoral thesis (M.D), UCL (University College London). Green open access

[thumbnail of out.pdf] Text
out.pdf

Download (16MB)

Abstract

Background: Deep hypothermic circulatory arrest (DHCA) can be useful during the repair of some heart defects in children, however it is associated with an increased incidence of neurological sequelae in the post-operative period. Following a period of DHCA the recovery of cerebral blood flow (CBF) and metabolism (CMRO2) are impaired. These changes may be a marker for cerebral injury since both CBF and CMRO2 recover normally when DHCA is not used. The aim of this series of experiments was to attempt to elucidate mechanisms of cerebral injury following DHCA and to determine possible strategies for neurological protection. Methods: All the experiments were undertaken in a neonatal piglet model (1-2 weeks old). The anaesthetic and circulatory arrest protocols used closely mimicked those employed clinically. In the first studies a variety of perfusion management strategies were followed by perfusion fixation of the brain for electron microscopic examination of the cerebral microvascular bed. The second series of experiments used the carbon black perfusion technique to enable visualisation of areas of no-reflow in the brain following DHCA. In the subsequent studies CBF and CMRO2 were determined with the radiolabelled microsphere technique. Five different strategies were used in an attempt to elucidate the mechanism of cerebral injury; leucocyte depletion, platelet activating factor (PAF) receptor antagonism, inhibition of lipid peroxidation, calcium channel blockade and finally free radical scavenging. Results: The ultrastructure of the cerebral microvascular bed following DHCA was characterised by perivascular, intracellular and organelle oedema, and vascular collapse. Intermittent perfusion during the arrest period resulted in a normal ultrastructural appearance. The second study demonstrated that DHCA does not prevent the no-reflow phenomenon from developing following ischaemia. In the remaining studies all the strategies studied, except leucocyte depletion, were associated with a significant improvement in cerebral recovery following DHCA compared to the control groups. Conclusions: The inter-related mechanisms causing cerebral impairment following DHCA are complicated. Cerebral recovery following DHCA is improved by free radical scavenging, PAF receptor antagonism, inhibition of lipid peroxidation and blockade of calcium entry into cells. Whether this will result in a reduction in neurological injury requires further investigation but the prospects would appear to be promising.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Mechanisms of cerebral injury and strategies for neuroprotection following deep hypothermic circulatory arrest in the neonatal piglet
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences; Neuroprotection
URI: https://discovery.ucl.ac.uk/id/eprint/10105687
Downloads since deposit
52Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item