CHRONIC HYPOXIC PULMONARY-HYPERTENSION - IS THROMBIN INVOLVED

Thrombin contracts vascular smooth muscle and stimulates its prolifera tion. Using a specific thrombin inhibitor, hirudin, we studied whether thrombin contributes to the pulmonary vasoconstriction and vascular p roliferation that occurs in pulmonary hypertension. Hirudin was infuse d intravenously (0.2 mg/h/kg) by minipumps in nine rats during a 3-wk exposure to hypobaric hypoxia (HH). Vehicle (normal saline) was infuse d in eight hypoxic control (HC) and seven normoxic control (NC) rats. Sufficient hirudin delivery was confirmed by a failure of undiluted pl asma from HH, but not from NC and HC, to clot in response to thrombin. When the plasma samples were diluted 1:10, the thrombin time was sign ificantly prolonged in HH when compared with that in both NC and HC. A lthough hirudin slightly reduced mean pulmonary arterial pressure in o pen-chest rats, there was no significant difference between the hypoxi c groups in total pulmonary resistance, right ventricle weight, morpho logic remodeling of lung vessels, or the perfusion pressure-flow relat ionship in isolated lungs. Vasoconstrictor responses of isolated lungs to angiotensin II and acute hypoxic challenges were not affected by h irudin treatment. We conclude that hirudin, in a dose sufficient to re duce thrombin's catalytic effect on fibrinogen, does not significantly prevent the development of chronic hypoxic pulmonary hypertension.