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Title: Haemodynamic studies in cirrhosis
Author: Jones, Alison Linda
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1996
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Study of the haemodynamic response to drugs is important in evaluation of their ability to achieve reduction of oesophageal variceal bleeding and to optimise their haemodynamic action in patients with liver disease. My studies have concentrated on the evaluation of two drugs, N-acetylcysteine and isosorbide-5-mononitrate (a drug reported to have a problem of tolerance). The portal and systemic haemodynamic response to low and high dose isosorbide-5-mononitrate (Is-5-Mn) was studied. 10 mg or 40 mg of oral Is-5-Mn was given acutely and chronically (bd for 4 weeks) allowing a 16 hour nitrate free interval to 25 patients with cirrhosis. Both doses of nitrate reduced the hepatic venous pressure gradient acutely and chronically, without evidence of tolerance by a reduction in the wedged hepatic venous pressure. The effect on mean asygos blood flow was dependent on the initial azygos blood flow, not on the dose of nitrate used; if low then vasodilation was seen in response to Is-5-Mn and vice-versa. As the effect of Is-5-Mn on cardiac output, systemic resistance and its pharmacokinetics in the presence of chronic liver disease has been previously reported this was not studied further. Intravenous N-acetylcysteine (NAC) was given to 11 patients with cirrhosis. There was no effect on mean heart rate or blood pressure despite a significant fall in systemic and pulmonary vascular resistance. Cardiac index increased but estimated liver blood flow and hepatic venous pressure gradients did not change significantly. Administration of NAC increased oxygen delivery but not arteriovenous oxygen extraction ratio or mean tissue oxygen consumption. Therefore NAC administration does not appear to confer haemodynamic benefit on patients with cirrhosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available