Since the disease chronic thrombo-embolic pulmonary hypertension (CTEPH), which is caused by an abnormal increase in blood pressure in the lungs due to obstructions, is still incompletely understood, therapeutic interventions are limited, and a curative medicine is still not available for CTEPH, we aim to unravel some mechanisms of this disease in this dissertation. To establish this, we developed a large animal model for CTEPH in which chronic catheters in and around the heart enable serial and awake measurements of blood pressures, cardiac output and oxygen metabolism both at rest and during exercise. The research in this thesis provides an insight in some of the underlying mechanisms which cause remodeling of the pulmonary vasculature and the heart in this disease. Our results indicate that specific research in global signaling pathways such as the vasodilator nitric oxide, the vasoconstrictor endothelin and Rho-kinase are very important for the development of more effective CTEPH treatment. In addition, we show the importance of exercise testing in PH, especially in the early stages to provide earlier diagnosis. All together we provided a lot of information on the pathophysiology of CTEPH with the help of a novel large animal model. Although we gathered all this information, future studies need to be conducted before the ideal, curative therapy will reach the patient.

Additional Metadata
Keywords chronic thrombo-embolic pulmonary hypertension, animal model, cardiac remodeling, pulmonary vascular remodeling, exercise
Promotor D.J.G.M. Duncker (Dirk) , D. Merkus (Daphne)
Publisher Erasmus University Rotterdam
Sponsor The studies described in this thesis were supported by Netherlands Cardiovascular Research Initiative; the Dutch Heart Foundation, the Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development and the Royal Netherlands Academy of Science. CVON (2012-08), PHAEDRA.
ISBN 978-94-6380-443-1
Persistent URL hdl.handle.net/1765/119534
Citation
Hoogestijn-Stam, K. (2019, September 24). A Novel Preclinical Model for Chronic Thrombo-Embolic Pulmonary Hypertension development, validation and characterization. Erasmus University Rotterdam. Retrieved from http://hdl.handle.net/1765/119534