Morphologic changes in explanted lungs after prostacyclin therapy for pulmonary hypertension

Eur J Med Res. 2006 May 5;11(5):203-7.

Abstract

Prostacyclin (PGI2) causes vasodilation and inhibition of platelet aggregation in vivo. PGI2 is also postulated to affect pulmonary vascular remodeling, at least partly through anti-proliferative effect via PGI2 receptor (PGIR). However, the mechanism(s) of action by which (PGI2) exerts its therapeutic effect is still not clear despite clear clinical benefit seen in severe pulmonary hypertension (PH) patients. We performed a histopathologic and morphometric study on the explanted lung tissues from PGI2-treated patients prior to lung transplantation (n = 9), in an attempt to elucidate morphologic changes associated with PGI2 treatment. Explanted lungs from PH patients without PGI2 treatment were examined as the control (n = 11). We also studied the possible differences in PGIR expression between the treated and untreated groups by immunohistochemical method. Seven out of 9 treated patients showed moderate to severe bronchial and perivascular inflammation, as opposed to only 1 such case in the control group. Five out of 9 treated cases showed moderate to severe alveolar edema with or without evidence of old hemorrhage, in contrast to only 1 case showing moderate alveolar edema in control patients. Morphometry did not reveal any significant difference between the two groups either in the % thickness of intima, media, or adventitia or in the density of plexiform lesions. Immunostain also failed to demonstrate any notable difference in PGIR expression. In conclusion, PGI2-treated cases revealed more pronounced pulmonary alveolar edema and inflammation, but no morphological evidence of altered vascular remodeling or PGIR expression after PGI2 therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antihypertensive Agents / therapeutic use*
  • Epoprostenol / therapeutic use*
  • Female
  • Humans
  • Hypertension, Pulmonary / drug therapy*
  • Inflammation
  • Lung / cytology
  • Lung / pathology*
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Pulmonary Artery / metabolism
  • Pulmonary Artery / pathology
  • Pulmonary Edema
  • Receptors, Epoprostenol / metabolism
  • Retrospective Studies

Substances

  • Antihypertensive Agents
  • Receptors, Epoprostenol
  • Epoprostenol