Endothelin abnormalities in patients with pulmonary embolism

Background: Endothelin (ET) is an endothelium-derived multifunctional peptide involved in the local regulation of the vascular tone. Study objectives: To assess changes of endogenous ET production/excretion in the acute phase (36 h from the event) of pulmonary embolism (PE). Participants: Ten patients with acute PE, nine patients with acute lung injury (ALI), and 12 healthy volunteers (HVs). Measurements and results: ET was detected by radioimmunoassay in venous and arterial blood as well as in 24-h urine specimens. For each subject, arterial/venous immunoreactive ET (ir-ET) ratio was evaluated as an index of its pulmonary extraction/synthesis. Creatinine clearance was employed in each case to obtain a corrected renal ir-ET clearance. Renal ir-ET clearance was comparable in all three groups. Arterial/venous ir-ET ratio was comparable in PE and in ALI patients (1.31+/-0.25 vs 1.24+/-0.20; p=0.7), while it was significantly higher in PE patients than in HV subjects (0.85+/-0.07; p=0.0001). Accordingly, 24-h urine ir-ET excretion was higher in PE (120.50+/-27.36 ng/24 h) and ALI patients (135.80+/-21.60 ng/24 h) than in HV subjects (88.33+/-9.31 ng/24 h; p=0.0001). Conclusions: Abnormalities of ET metabolism-mainly related to increased synthesis and/or defective pulmonary handling-occur in the acute phase of PE. The relevance of this finding with respect to the pathogenesis and/or management of pulmonary thromboembolism remains to be elucidated.