Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension

Ronit Friedman, J. Gregory Mears, Robyn J. Barst

Research output: Contribution to journalArticle

138 Citations (Scopus)

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. Methods and 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 (1.1±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.

Original languageEnglish (US)
Pages (from-to)2782-2784
Number of pages3
JournalCirculation
Volume96
Issue number9
StatePublished - Nov 4 1997
Externally publishedYes

Fingerprint

Cell Aggregation
Epoprostenol
Platelet Aggregation
Endothelial Cells
Wounds and Injuries
von Willebrand Factor
Factor VIII
Familial Primary Pulmonary Hypertension
Lung
Blood Coagulation Factors
Thrombophilia
Vascular System Injuries
Arterioles
Vasodilator Agents
Endothelium
Blood Vessels
Hemodynamics
Survival

Keywords

  • Coagulation
  • Endothelium-derived factors
  • Platelets
  • Prostaglandins
  • Pulmonary heart disease

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension. / Friedman, Ronit; Gregory Mears, J.; Barst, Robyn J.

In: Circulation, Vol. 96, No. 9, 04.11.1997, p. 2782-2784.

Research output: Contribution to journalArticle

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AU - Friedman, Ronit

AU - Gregory Mears, J.

AU - Barst, Robyn J.

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N2 - 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. Methods and 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 (1.1±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.

AB - 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. Methods and 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 (1.1±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.

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KW - Endothelium-derived factors

KW - Platelets

KW - Prostaglandins

KW - Pulmonary heart disease

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