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Title: Cardiopulmonary interactions of hypoxia and hypercapnia and the role of vasoactive mediators in the pulmonary circulation in man
Author: Kiely, David Gerard
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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We have examined the cardiopulmonary effects of hypoxia and hypercapnia in the integrated physiological system of normal man using non-invasive pulsed-wave Doppler echocardiography and phonocardiography and have extended this work to study the role vasoactive mediators in the pulmonary circulation in man. We have demonstrated that systolic and diastolic function are unaffected by acute hypercapnia in normal man. Acute hypoxaemia significantly impairs both right and left ventricular diastolic function, in a dose dependent manner, although systolic function remains well preserved. In addition to confirming that hypoxia is a potent pulmonary vasoconstrictor we have demonstrated that hypercapnia is a weak pulmonary vasoconstrictor, suggesting a possible role in ventilation perfusion matching in health and disease. We have also shown potentially adverse electrophysiological effects of both hypoxia and hypercapnia, the clinical significance of which is unknown. The second part of this thesis examines the roles of vasoactive mediators in the pulmonary circulation. In a series of placebo controlled studies we have demonstrated for the first time in normal man that angiotensin II is capable of modulating the acute hypoxic pulmonary vasoconstrictor response, using infusions of the non selective angiotensin II receptor blocker saralasin and the orally active type I angiotensin II receptor blocker losartan. We have extended this work to patients with hypoxaemic cor pulmonale secondary to chronic obstructive pulmonary disease (COPD) and have shown beneficial haemodynamic and endocrine sequelae of type 1 angiotensin II receptor blocking in these patients with a vasoreactive pulmonary circulation. These results suggest that manipulation of the renin-angiotensin system may be of therapeutic benefit in this patient group. We have shown that acute hypoxaemia is a stimulus to endothelin-1 release in normal man and that levels of this peptide are elevated in patients with hypoxaemic cor pulmonale due to COPD.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available