Background: To assess the pathophysiological response in pulmonary embolism, we established a novel model using
a certain volume of relatively small thrombi in mice.
Methods: Thrombi with a maximum diameter of 100 µm or 500 Goudy Old Stylem were administered intravenously
under anesthesia, and the survival ratio was evaluated at 4 hours. The thrombus location, hemodynamics and
Computed Tomography (CT) angiography was assessed after thrombus administration. In addition, quantification
of cytokine mRNAs and immunohistochemical analysis for interleukin (IL)-6 and CD68 as a macrophage marker
were also performed in normal and embolized lungs at 4 hours.
Results: Mice with 100 µm clots showed a dose-dependent survival between 2.3 µL/g and 3.0 µL/g 4 hours after
embolization. The thrombi were located at the peripheral region of the lung, which was consistent with the disruption
of blood circulation. In CT angiography analysis, approximately 60% of vessels with a diameter of less than 100
µm was occluded in these mice. IL-6 and tumor necrosis factor alpha mRNA were significantly higher and lower,
respectively, in embolized lungs than in normal lungs at 4 hours. In both the normal and embolized lungs, IL-6 was
expressed in CD68-positive macrophages, and their numbers were comparable.
Conclusion: These results show that the pulmonary embolism model induced by a certain amount of small clot is
highly reproducible and useful for evaluating pathophysiological responses in the embolized lung. Furthermore, it
was found that inflammatory responses shown by IL-6 increase may contribute to the pathogenesis in early stage of
pulmonary embolism.