Chronic hypoxic pulmonary hypertension. Is thrombin involved?
Chronic hypoxic pulmonary hypertension. Is thrombin involved?
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慢性缺氧性肺动脉高压。
DOI：
10.1164/ajrccm/148.4_pt_1.1043
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Weir,EK
中科院分区：
文献类型：
--
作者：
Hampl,V;Archer,SL;Bach,R;Nelson,DP;Weir,EK
Thrombin contracts vascular smooth muscle and stimulates its proliferation. Using a specific thrombin inhibitor, hirudin, we studied whether thrombin contributes to the pulmonary vasoconstriction and vascular proliferation that occurs in pulmonary hypertension. Hirudin was infused intravenously (0.2 mg/h/kg) by minipumps in nine rats during a 3-wk exposure to hypobaric hypoxia (HH). Vehicle (normal saline) was infused in eight hypoxic control (HC) and seven normoxic control (NC) rats. Sufficient hirudin delivery was confirmed by a failure of undiluted plasma 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 significantly prolonged in HH when compared with that in both NC and HC. Although hirudin slightly reduced mean pulmonary arterial pressure in open-chest rats, there was no significant difference between the hypoxic groups in total pulmonary resistance, right ventricle weight, morphologic remodeling of lung vessels, or the perfusion pressure-flow relationship in isolated lungs. Vasoconstrictor responses of isolated lungs to angiotensin II and acute hypoxic challenges were not affected by hirudin treatment. We conclude that hirudin, in a dose sufficient to reduce thrombin's catalytic effect on fibrinogen, does not significantly prevent the development of chronic hypoxic pulmonary hypertension. Hampl V, Archer SL, Bach R, Nelson DP, Weir EK. Chronic hypoxic pulmonary hypertension: is thrombin involved? Am Rev Respir Dis 1993; 148: 1043-8.Chronic hypoxia, resulting from obstructive lung diseases or from high altitude exposure, produces pulmonary hypertension. Chronic hypoxic pulmonary hypertension is characterized by pulmonary vasoconstriction (1, 2), pulmonary vascular smooth muscle and fibroblast proliferation (3), and increased turnover and amount of connective tissue in pulmonary vessels (4-6). Associated with pulmonary hypertension is right ventricular hypertrophy. The mechanism of the development of chronic hypoxic pulmonary hypertension is not clear. There are findings to indicate that elements of the blood coagulation cascade might be involved. Pulmonary intravascular microthrombi have been reported in rats exposed to chronic hypoxia (7). Thrombocytopenia is common in both animal models (8) and patients (9) with hypoxic pulmonary hypertension. A widely used anticoagulant, heparin, reduces chronic hypoxic pulmonary hypertension in several animal models (10-14).
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