title: Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension.
abstract: BACKGROUND
  Primary pulmonary hypertension (PPH) is characterized by vascular injury of pulmonary arterioles, in which endothelial dysfunction may play a major role. Although continuous infusion of prostacyclin (prostaglandin I2, a potent vasodilator released by vascular endothelial cells) improves the clinical status and survival in PPH, its mechanism or mechanisms of action remain unclear.
  
  
  RESULTS
  We measured endothelium-derived clotting factors and assayed platelet aggregation in 64 patients (26 adults and 38 children) with PPH before long-term PGI2 therapy. Repeat studies were performed in 42 patients (18 adults, 24 children) after one year of PGI2 therapy. At baseline, 87% of adults and 79% of children had abnormal platelet aggregation. In addition, factor VIII, von Willebrand (vW) antigen, and ristocetin cofactor levels were abnormally high in 92%, 72%, and 52%, respectively, of the adults versus 29%, 16%, and 16%, respectively, of the children (P<.005 adults versus children). With long-term PGI2, platelet aggregation normalized in 83% of the adults and 80% of the children who had platelet aggregation abnormalities at baseline (P<.01). Factor VIII, vW antigen, and ristocetin cofactor also decreased with long-term PGI2 in both groups (P<.02). The ratio of ristocetin cofactor to vW antigen, which may reflect biological activity of vW factor, increased with long-term PGI2 in adults from an abnormally low level (0.6+/-0.2) to normal level (1.10+/-0.4), and in children the ratio increased from 0.8+/-0.3 to 1.3+/-0.4 (normal, 0.8 to 1.4).
  
  
  CONCLUSIONS
  Alterations in the coagulation system may contribute to the pathogenesis of PPH; the normalization of these endothelial markers concomitant with improvement in hemodynamic parameters with long-term PGI2 suggests that long-term PGI2 remodels the pulmonary vascular bed with subsequent decreases in endothelial cell injury and hypercoagulability.
authors.affiliation: Department of Pediatrics, Columbia University College of Physicians & Surgeons, New York, NY 10032, USA.
authors.forename: R
authors.initials: R
authors.lastname: Friedman
authors.forename: J G
authors.initials: JG
authors.lastname: Mears
authors.forename: R J
authors.initials: RJ
authors.lastname: Barst
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D011464:Epoprostenol / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000188:drug therapy; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D014665:Vasodilator Agents; D011464:Epoprostenol