Regulation of Pulmonary Vascular Tone in Health and Disease: Special emphasis on exercise and pulmonary hypertension after myocardial infarction
(Regulatie van de pulmonale vaattonus in gezondheid en ziekte Met de nadruk op inspanning en pulmonale hypertensie na een hartinfarct)
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High bloodpressure in the pulmonary circulation is called pulmonary hypertension (PH). In patients with PH, the balance between vasodilators and vasoconstrictors is disturbed. PH is an important cause of death; it is characterized by elevated levels of pulmonary artery pressure and pulmonary vascular resistance. Secondary PH occurs after myocardial infarction and is often the cause of eventual right ventricular failure. To treat PH it is important to understand the regulation of the healthy pulmonary vascular bed and the alterations in PH after myocardial infarction (MI). In this thesis these questions are investigated in healthy swine and in swine with post-MI PH. These studies were performed under resting conditions but also during exercise, because the right ventricle and the pulmonary circulation are the main determinants of exercise capacity. By improving the exercise capacity, quality of live will improve for these patients. In our studies different p! arameters such as pressure and resistance are being investigated. The most important findings in this thesis are that endothelin and nitric oxide are increased during exercise in healthy swine, while the contribution of prostanoids remains unchanged. After MI, the balans between vasoldilators and vasoconstrictors is disturbed, which results in increased pulmonary artery pressure and increased pulmonary vascular resistance. The contributions of endothelin and prostacylin are increased. The vasodilating by inhibition of phosphodiesterase 5 is also increased after MI. In this thesis some current used therapies for patienst with post-MI PH (endothelin receptor blockers and phosphodiesterase 5 inhibition) are used to investigate the pulmonary circulation.
Netherlands Heart Foundation
Duncker, Prof. Dr. D.J.G.M. (promotor)