An investigation of GTN and NO related therapeutics in the treatment of acute stroke
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...
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| Format: | Thesis (University of Nottingham only) |
| Language: | English |
| Published: |
2007
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| Online Access: | https://eprints.nottingham.ac.uk/10305/ |
| Summary: | 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. |
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