Rodent models of pulmonary embolism and chronic thromboembolic pulmonary hypertension

Pulmonary embolism (PE) is the third most prevalent cardiovascular disease. It is associated with high in-hospital mortality and the development of acute and chronic complications. New approaches aimed at improving the prognosis of patients with PE are largely dependent on reliable animal models. Mice, rats, hamsters, and rabbits, are currently most commonly used for PE modeling because of their ethical acceptability and economic feasibility. This article provides an overview of the main approaches to PE modeling, and the advantages and disadvantages of each method. Special attention is paid to experimental endpoints, including morphological, functional, and molecular endpoints. All approaches to PE modeling can be broadly divided into three main groups: 1) induction of thromboembolism, either by thrombus formation in vivo or by injection of in vitro prepared blood clots; 2) introduction of particles of non-thrombotic origin; and 3) surgical procedures. The choice of a specific model and animal species is determined based on the objectives of the study. Rodent models of chronic thromboembolic pulmonary hypertension (CTEPH), which is the most devastating complication of PE, are also described. CTEPH models are especially challenging because of insufficient knowledge about the pathogenesis and high fibrinolytic activity of rodent plasma. The CTEPH model should demonstrate a persistent increase in pulmonary artery pressure and stable reduction of the vascular bed due to recurrent embolism. Based on the analysis of available evidence, one might conclude that currently, there is no single optimal method for modeling PE and CTEPH.