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Development of the bronchial and vascular smooth muscle and the effects of pulmonary hypertension

Schindler, Margrid Brigitte; (2004) Development of the bronchial and vascular smooth muscle and the effects of pulmonary hypertension. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Episodes of pulmonary hypertension are characterised by rapid increases in pulmonary arterial pressure and a clinical impression of stiff lungs. The aim of this study was to examine normal development and the effect of pulmonary hypertension on the airways, pulmonary arteries and veins to test the hypothesis that there are related changes in bronchial and pulmonary arterial smooth muscle. Method: Pulmonary mechanics were measured in ventilated infants with pulmonary hypertension and findings compared to those in non-hypertensive infants. Using porcine and human post mortem material, morphometry of bronchial and pulmonary arterial smooth muscle was performed on normal and pulmonary hypertensive tissue. Isolated pulmonary arteries, veins and bronchi were studied using organ bath pharmacology. The effects of Endothelin-1, noradrenaline and Electrical Field Stimulation (EPS) on the normal neonatal and pulmonary hypertensive lung, during hypertension and after recovery, were examined. Results: In pulmonary hypertensive infants, airway resistance was increased during episodes of pulmonary hypertension, and bronchial and vascular smooth muscle was increased two fold. Using the porcine developmental and hypoxic pulmonary hypertension model, the Endothelin-1 and EPS contractile effect was greater in the pulmonary arteries and bronchi during fetal life and in the presence of pulmonary hypertension. Evidence for parallel impairment of pulmonary arterial and bronchial adrenoceptor and EPS mediated vaso and broncho-relaxation was found in early development and during pulmonary hypertension, but the veins were largely unaffected. There was evidence of pulmonary arterial endothelial and bronchial epithelial impairment in fetal life and during pulmonary hypertension. Endothelium dependent relaxation was also impaired in the pulmonary hypertensive human infants. Normoxic recovery occurred more rapid in pulmonary arteries than bronchi. Conclusion: The findings support the concept of parallel responses in bronchi and pulmonary arteries in development and during pulmonary hypertension and suggests a role for treatments which benefit both structures.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Development of the bronchial and vascular smooth muscle and the effects of pulmonary hypertension
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Pulmonary hypertension
URI: https://discovery.ucl.ac.uk/id/eprint/10107377
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