title: Pathophysiology and treatment of haemodynamic instability in acute pulmonary embolism: the pivotal role of pulmonary vasoconstriction.
abstract: Acute massive pulmonary embolism has a high mortality rate. Fatal haemodynamic deterioration is caused by an acute increase in pulmonary vascular resistance. Traditionally, the degree of mechanical obstruction of the pulmonary vasculature by the embolic thrombus is considered to be the major determinant of this increase in right ventricular afterload. However, there is evidence to suggest that another factor plays an important role, since there is a marked discrepancy between the haemodynamic manifestations of acute pulmonary embolism and the degree of mechanical obstruction. Historic studies indicate that this discrepancy is largely explained by pulmonary vasoconstriction caused by vasoactive mediators, released mainly by activated platelets. Thromboxane-A(2) and serotonin are probably the two most important pulmonary vasoconstrictors in this context. Antagonising their effects dramatically increases tolerance to experimental pulmonary embolism in animals. In humans, this concept should eventually find its way into clinical practice. In the future, acute massive pulmonary embolism could be treated with antagonists to pulmonary vasoconstrictors, or with direct pulmonary vasodilators.
authors.affiliation: Department of Internal Medicine, Academic Medical Center, Suite F4-222, 9, 1105 AZ, Meibergdreef, The Netherlands. y.m.smulders@amc.uva.nl
authors.forename: Y M
authors.initials: YM
authors.lastname: Smulders
mesh_terms: D000208:Acute Disease; D000818:Animals; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D015539:Platelet Activation; D011655:Pulmonary Embolism / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists / Q000627:therapeutic use; D013045:Species Specificity; D013928:Thromboxane A2 / Q000378:metabolism; D014655:Vascular Resistance; D014661:Vasoconstriction; D014665:Vasodilator Agents / Q000627:therapeutic use
chemical_list: D005343:Fibrinolytic Agents; D012702:Serotonin Antagonists; D014665:Vasodilator Agents; D012701:Serotonin; D013928:Thromboxane A2