ABSTRACT
To understand the hemodynamic alterations associated with chronic thromboembolic pulmonary hypertension, the large pulmonary arteries of mongrel dogs were chronically obstructed with lysis-resistant thrombi. Pulmonary hemodynamics were experimentally measured and described by multipoint pulmonary arterial pressure (PAP) vs. flow plots. In nine anesthetized chronically embolized dogs, but not in six control dogs, the PAP-flow line shifted significantly upward in a parallel fashion by 4.2 +/- 0.7 mmHg. The postembolic pulmonary circulation was further characterized by predictions from a morphometric-based elastic tube and sheet flow model of the canine pulmonary circulation. After model validation with the preembolic PAP-flow data, the derived postembolic PAP matched the in vivo results to within 1 mmHg. A detailed analysis of the model-derived PAP drop revealed that the PAP-flow line shift can be accounted for by a novel fixed resistor in the largest obstructed pulmonary artery.
Subject(s)
Blood Pressure , Pulmonary Artery/physiopathology , Pulmonary Circulation , Thromboembolism/physiopathology , Animals , Chronic Disease , Dogs , Forecasting , Hypertension, Pulmonary/etiology , Models, Cardiovascular , Thromboembolism/complicationsABSTRACT
BACKGROUND: Many questions remain regarding the pathogenesis, natural history, diagnosis, and treatment of chronic thromboembolic pulmonary hypertension in patients. To answer such questions, we developed an animal model of this disorder. The brisk thrombolytic response of canines to acute embolism has, previously, prevented the establishment of such a model. METHODS AND RESULTS: The fibrinolytic inhibitor tranexamic acid was given orally to canines before, and for intervals after, pulmonary emboli were released from venous thrombi formed in vivo in femoral veins or the inferior vena cava. Preliminary studies disclosed that embolic residuals from femoral vein thrombi were not sufficient to cause significant, persistent pulmonary hypertension. With repetitive, larger thrombi embolized from the inferior vena cava, however, persistent pulmonary hypertension was achieved in most animals. CONCLUSIONS: 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.
