Abstract 051: A New Model of Murine Stasis Pulmonary Thromboembolism in vivo With Assessment by Noninvasive Multimodal Molecular-Structural Imaging
| Autor: | Farouc A. Jaffer, Chase W. Kessinger |
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| Rok vydání: | 2018 |
| Předmět: | |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 38 |
| ISSN: | 1524-4636 1079-5642 |
| Popis: | Objective: Pulmonary embolism (PE) is a life-threatening cardiovascular disease that urgently requires improved diagnostic, prognostic and therapeutic options. Here we established and investigated a novel murine PE model based on embolization of a stasis-induced venous thrombus (VT). We further utilized in vivo molecular-structural imaging of fibrin accessibility to assess the healing status of the PE. Methods: Stasis VT was induced in the femoral veins of donor C57BL6 mice. VT was resected 24 hours (h) after induction and then intravenously injected into recipient mice to create PE. Pulse-wave Doppler of pulmonary artery flow was utilized to evaluate the pulmonary arterial pressure (PAP) before and 24h after embolization. One day after embolization, the fibrin-specific probe FTP11-CyAm7 (750/767nm ex/em, 150 nmoles/kg i.v.) assessed the FTP binding and spatial localization of PE via integrated fluorescence-mediated tomography and computed tomography (FMT-CT) pulmonary angiography. Mice were sacrificed 1, 4, 8, or 21 days following stasis-VT embolization, and underwent histological analysis of the PE. Results: Femoral vein stasis-VT exhibited similar temporal inflammatory neutrophil and monocyte/macrophage infiltration and FTP11 binding (fibrin accessibility) kinetics compared to inferior vena cava stasis-VT models. The mean VT width and length were 2.4±0.2mm and 0.65±0.02mm, respectively (n=29 thrombi). Noninvasive ultrasound assessment of the mouse PAP, assessed via the pulmonary acceleration time (PAT), showed a 22% decrease (p=0.03) in pre-to-post-PE PAT times, consistent with increased PAP due to PE. FMT-CT imaging using FTP11 demonstrated accessible fibrin in day 1 PE and visualized PE confined to the lungs, primarily (91%) in the right lung. Ex vivo fluorescence reflectance imaging and histological analysis verified the location PE reported by FMT-CT. Conclusions: These data validate the first in vivo model of PE based on stasis VT formed in vivo. The model reproducibly generates a survival PE that harbors accessible fibrin in recent stasis VT lodged in the lung, and acute increases PAP. This new clinically relevant model of PE is anticipated to facilitate research of acute PE and chronic thromboembolic pulmonary hypertension. |
| Databáze: | OpenAIRE |
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