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Title: The effect of the calcium antagonist, nimodipine, on local cerebral blood flow, glucose use and focal cerebral ischaemia
Author: Mohamed, Awni A.
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1985
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Nimodipine (a dihydropyridine derivative) is one of a range of compounds which have been termed calcium antagonists, and whose pharmacological efficacy may result partly from an ability to inhibit the slow inward current of calcium ions in cell membranes. Nimodipine is a potent dilator of cerebral vessels in vitro and in situ, and this has stimulated interest in its effect on normal cerebral circulation and its use in cerebral ischaemia. In the studies that form this thesis, I have examined several aspects of the effect of nimodipine on the cerebral circulatory responses in normal brain and in the presence of a well defined focal ischaemic lesion induced by occlusion of the middle cerebral artery (MCA). The effect of the calcium antagonist, nimodipine, on local cerebral blood flow (CBF) in 31 regions of the CNS was studied with the [14C]-iodoantipyrine autoradiographic technique in lightly anaesthetised, mechanically ventilated rats. Continuous intravenous infusion of nimodipine (1, 2 or 4 mug kg-1min-1) produced a dose-dependent reduction in mean arterial blood pressure (MABP) (reduced by 26 +/- 2% after 30 min of nimodipine, 4 mug kg-1min-1) and a significant elevation in plasma glucose concentration (increased by 44 +/- 2% after 30 min of nimodipine, 4 mug kg-1min-1). Local CBF was increased significantly during infusions of nimodipine (1 mug kg-1min-1) in 9 of the 31 regions examined, e.g. , the parietal cortex (by 108%), sensory-motor cortex (by 132%), auditory cortex (by 78%), frontal cortex (by 65%). In contrast to the increases in CBF observed in forebrain regions, no significant increases in CBF were observed during nimodipine infusion in regions of the lower brain stem, cerebellum and pons, or in myelinated fibre tracts. The proportionately greatest increases in local CBF were observed during infusion of the lowest dosage of nimodipine (1 mug kg-1min-1), suggesting either that this dosage provokes maximum cerebrovascular relaxation or that effects of increasing concentrations are counteracted by the concomitant systemic hypotension. The findings of this series of experiments emphasise that the dose must be regulated very carefully to avoid hypotension and hyperglycaemia; with calcium antagonists, correct dose selection may therefore be critical.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available