It is well known that endothelin (ET)-1 mediates vascular remodelling in various kinds of clinical and experimental pulmonary hypertension. The aim of this study was to investigate whether ET-1 is associated with the development of pulmonary vascular remodelling in a canine model of chronic embolic pulmonary hypertension.Pulmonary hypertension was induced in 10 mongrel dogs by repeated embolization with ceramic beads. In five of the dogs, bosentan, a nonselective ET receptor antagonist, was administered throughout the study. Haemodynamic measurements and plasma ET-1 assays were performed every 2 months. Eight months after initial embolization, computer-assisted morphometry and immunohistochemistry were performed on the lung tissue including that from three control dogs.Pulmonary arterial pressure and pulmonary vascular resistance were increased in all embolized dogs, compared to baseline. In nontreated embolized dogs, plasma ET-1 concentration and pulmonary arterial wall thickness were increased compared to control animals, and ET-1 immunoreactivity was detected in thickened pulmonary arteries. In bosentan treated dogs, pulmonary arterial walls were not significantly thickened.Pulmonary vascular remodelling, associated with elevated plasma endothelin-1 levels and positive endothelin-1 immunoreactivity in lung tissue is attenuated by the endothelin receptor antagonist, bosentan. These findings suggest that endothelin mediates pulmonary vascular remodelling in a canine model of chronic embolic pulmonary hypertension. Eur Respir J 2000; 15: 640±648. There is increasing evidence that remodelling occurs in the pulmonary vascular bed of patients with chronic thromboembolic pulmonary hypertension (CTEPH) and may contribute to the progression of the disease [1±5]. The mechanisms responsible for this remodelling are, however, poorly understood.Endothelin (ET)-1 is a potent endogenous vasoconstrictor in the pulmonary circulation and also a growth factor in the pulmonary vasculature [6]. These constrictor and proliferative responses are mainly mediated by ET A receptors [7,8], and blocked by selective and nonselective antagonists [9,10]. Previous studies have shown that ET-1 is upregulated in the lungs of primary and secondary pulmonary hypertensive patients [11±13], and ET antagonists have been shown to attenuate the development of pulmonary vascular remodelling and pulmonary hypertension (PH) in various animal models [14±16]. In the CTEPH, however, the role of ET-1 is still unclear.Using a canine model of thromboembolic PH, which the authors have previously developed [17,18], this study was performed to: 1) see whether pulmonary vascular remodelling occurs in a canine model of chronic embolic pulmonary hypertension (CEPH); 2) examine the changes of ET-1 in association with the development of CEPH; and 3) evaluate the effects of bosentan, a nonselective ET receptor antagonist, on pulmonary vascular remodelling in CEPH. Material and methods Study animalsA total of 10 mongrel dogs (body weight 19±23 kg) were used ...

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Resolution of emboli in the canine can be inhibited by tranexamic acid. As in humans, a spectrum of embolic residuals is encountered, and the perfusion lung scan consistently underestimates the extent of embolic residuals. Studies of this animal model continue.

Radiolabeled anti-beta noninvasively distinguishes propagating thrombi from those stabilized by anticoagulants. They may be useful for detecting thrombosis clinically as well as for monitoring the efficacy of anticoagulation.