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Title: Haemodynamic disturbance in cirrhosis : a study of humoral mediators and implications for therapy
Author: Forrest, E. H.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1997
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Many complications of cirrhosis of the liver can be related to the haemodynamic disturbance associated with this condition. Patients with cirrhosis have a variety of circulatory anomalies: portal hypertension, systemic hypotension, systemic vasodilatation and renal vasoconstriction being characteristic. This thesis set out to clarify the causes and possible treatments of these disturbances. Investigations were carried out by studying the regional haemodynamics of patients with cirrhosis using vascular catheters, and also by studying the platelets from such patients as models of vascular smooth muscle cell reactivity. In particular the roles of nitric oxide and adenosine were studied. Nitric oxide synthase inhibition led to an improvement in the mean arterial pressure presumably by increasing systemic vascular resistance without affecting the portal or porto-systemic circulations. Adenosine receptor blockade reduced portal pressure slightly but did not improve the hyperdynamic circulation of cirrhosis. However renal perfusion, both in absolute terms and as a proportion of cardiac output, improved significantly. Plasma from patients with cirrhosis was found to possess a factor(s) which reduces platelet cytosolic calcium. This induced signal transduction defect may reflect changes in vascular tissue in cirrhosis. Nitric oxide synthase inhibition partly ameliorated this by increasing basal cytosolic calcium in platelets from patients with cirrhosis. Adenosine receptor blockade did not affect the cytosolic calcium of platelets. The pharmacological manipulation haemodynamics was also studied. Propranolol lowered portal pressure by reducing portal vein inflow. Isosorbide-5-mononitrate mediated its portal hypotensive effect by reducing intra-hepatic vascular resistance. Carvilol, a vasodilating beta-blocker, lowered portal pressure significantly without compromising renal perfusion. However patients with ascites were more susceptible to systemic hypotension. In conclusion nitric oxide appears to have a role as a significant systemic vasodilator, whilst adenosine is a potent renal vasoconstrictor in cirrhosis. Vasodilating beta-blockers may have an important role in the treatment of portal hypertension.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available