An investigation of GTN and NO related therapeutics in the treatment of acute stroke

Willmot, Mark (2007) An investigation of GTN and NO related therapeutics in the treatment of acute stroke. DM thesis, University of Nottingham.

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Abstract

Background: High blood pressure is common in acute stroke and has been linked with

poor outcome. Hence, outcome might be improved by lowering blood pressure. This

thesis investigates the potential for glyceryl trinitrate, a nitric oxide donor, for lowering

blood pressure in acute stroke. Methods: A systematic review was employed to clarify

the relationship between outcome and BP in observational studies. Next two systematic

reviews of animal studies using nitric oxide therapeutics in experimental stroke were

performed to assess the effects on infarct volume and cerebral perfusion. Finally, two

randomised controlled clinical trials of glyceryl trinitrate were performed in acute stroke

patients to measure the systemic and cerebral haemodynamic effects. Results: In

observational studies high blood pressure in acute stroke was associated with

subsequent death, death or dependency, and death or deterioration. In experimental

stroke nitric oxide sources and selective nitric oxide synthase inhibitors significantly

reduced stroke volume. Glyceryl trinitrate lowered peripheral and central blood pressure

and increased aortic compliance when given <48 hours from stroke. Glyceryl trinitrate did

not alter quantitative measures of cerebral perfusion despite significantly lowering blood

pressure <5 days from stroke. Conclusion: High blood pressure is a therapeutic target in

acute stroke and animal data support the use of nitric oxide sources for lowering blood

pressure. It is feasible to use glyceryl trinitrate for this purpose since it does not

compromise cerebral perfusion. Trials now need to urgently assess the effect of lowering

BP on outcome.

Item Type:Thesis (DM)
Supervisors:Bath, Philip Michael William
Uncontrolled Keywords:Stroke Medicine
Faculties/Schools:UK Campuses > Faculty of Medicine and Health Sciences > School of Clinical Sciences > Former School of Medical and Surgical Sciences
ID Code:305
Deposited By:Mark Willmot
Deposited On:23 Oct 2007
Last Modified:06 Feb 2009 14:43

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