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Title: Peripheral haemodynamic studies in patients with cirrhosis and portal hypertension
Author: Salem, Ahmed Helmy
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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In patients with cirrhosis and matched healthy controls, bilateral forearm blood flow (FBF) was measured using venous occlusion plethysmography at baseline, and after unilateral sub-systemic, intra-brachial infusions of incremental doses of agonists or selective receptor antagonists, with or without the application of lower body negative pressure (LBNP) or 'NO-clamp': a balanced co-infusion of L-NMMA (a NO synthase inhibitor) and sodium nitroprusside (an exogenous NO donor) to block endogenous NO release and restore normal basal blood flow respectively. Baseline haemodynamic parameters, and plasma hormonal concentrations, were also measured using electrical bioimpedance and radioimmunoassay respectively. Noradrenaline, angiotensin II, endothelin-1, BQ-788 (a selective endothelin type B receptor antagonist), and L-NMMA reduced FBF and, whilst responses to noradrenaline, BQ-788, and L-NMMA were similar across groups, those to ANG II and endothelin-1 were greater in the healthy controls than in patients with cirrhosis. Both losartan (a selective ANG II type 1 receptor antagonist) and BQ-123 (a selective endothelin type A receptor antagonist) increased FBF, but responses to losartan were enhanced only in patients with advanced cirrhosis, and those to BQ-123 were enhanced in patients with pre-ascitic cirrhosis. LBNP caused similar reductions in FBF during both saline and losartan infusions. However, responses to LBNP were less in patients with advanced cirrhosis only. In the presence of the 'NO-clamp', the ANG II mediated vasoconstriction was enhanced in patients with cirrhosis, unchanged in controls, and became similar in both groups. In contrast, the BQ-123-induced vasodilatation was abolished in controls and attenuated in patients during the 'NO-clamp', with FBF remaining significantly greater in patients with cirrhosis. These studies indicate that ANG II contributes to the maintenance of basal peripheral vascular tone only in advanced cirrhosis, but not to sympathetically-stimulated vascular tone. The impaired responses to ANG II and endothelin-1 are apparent in early cirrhosis, whilst those to LBNP are impaired only in advanced cirrhosis despite normal responses to noradrenaline infusion.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available