PARTIAL REVERSAL OF HYPOXIC PULMONARY-HYPERTENSION BY HEPARIN

Chronic hypoxia produces pulmonary hypertension and an increase in medial thickness of pulmonary arteries that reach maximal values after 10 days of hypoxia. We previously showed that heparin given during the first 10 days of hypoxia reduced the development of both pulmonary hypertension and vascular remodeling in the guinea pig. To determine if heparin could reverse established hypoxic pulmonary hypertension and vascular remodeling, we administered heparin by continuous subcutaneous infusion (20 U/kg/h) for the last 7 days of a 21-day exposure to hypoxia (10% O2, balance N2) and compared these animals with normal saline-infused hypoxic control and room air-exposed animals. Hypoxia increased pulmonary artery pressure from 11 +/- 1 mm Hg (mean +/- SEM) in room air animals to 20 +/- 2 mm Hg (p < 0.05) in saline-treated hypoxic control animals. Heparin reduced pulmonary artery pressure to 16 +/- 1 mm Hg (p < 0.05 versus hypoxic control and room air control animals). Total pulmonary resistance (TPR) increased with hypoxia from 0.043 +/- 0.003 mm Hg x min x kg-1 x ml-1 in room air to 0.090 +/- 0.004 in hypoxia (p < 0.05), and in the rise in TPR was also partially reversed by heparin to 0.068 +/- 0.0003 (p < 0.05). The percentage of medial thickness of alveolar duct arteries increased from 5.8 +/- 0.6% in room air to 9.5 +/- 0.1% (p < 0.05) after 3 wk of hypoxia, and heparin therapy partially reversed the increase in medial thickness to 7.2 +/- 0.7% (p < 0.05 versus both hypoxia control and room air). Hematocrit increased with hypoxia and was not significantly different in hypoxic control or heparin-treated groups (56 +/- 3 versus 50 +/- 4, respectively, p < 0.05). We conclude that heparin, at doses that previously have been shown to impair the development of hypoxic pulmonary hypertension and vascular remodeling, may also partially reverse these changes once fully established.