The clotting process is fundamental to hemostasis, yet it can also lead to devastating complications in vascular disease progression, compromised interventional procedures, and failure of implanted cardiovascular devices. Perhaps most notable of the devastating complications of intraluminal thrombus is the acute occlusion of a coronary artery following rupture of a vulnerable plaque, which can cause sudden death. In addition, however, ~75% of abdominal aortic aneurysms involve an intraluminal thrombus, which is thought to adversely affect the biomechanics of the aneurysmal wall as well as biochemical processes related to chronic inflammation and oxygen transport to the media;~21% of interventional coil treatments of intracranial saccular aneurysms fail, apparently due to the lack of """"""""maturation"""""""" of the induced intraluminal clot;and severity of cerebral vasospasm, the leading cause of morbidity and mortality in patients surviving the rupture of an intracranial aneurysm, correlates strongly with clot burden and clot clearance rates. Intraluminal thrombus also continues to be one of the limiting concerns in the design and use of many implanted cardiovascular devices, including stents, heart valves, and in-line vascular assist devices. Given that the structural integrity, or lack thereof, of the intraluminal thrombus is fundamental to its role in these and many other examples of cardiovascular disease and treatment, there is a pressing need to understand better the underlying biomechanics. All past studies of the mechanical properties of blood clots have focused on either newly formed, primarily fibrin-based, clots or mature clots having an unknown natural history that were obtained from patients. We will be first, therefore, to quantify, model, and correlate the evolving composition, structure, and properties of intraluminal clots in a novel, well controlled in vivo model. Toward this end, we will be the first to use a structurally-motivated constrained mixture theory that accounts naturally for the evolution of mechanical properties of materially nonuniform tissues, including possible mechano-stimulated compaction of the newly synthesized collagen. We submit that both data and model will fill important gaps in our understanding and thereby provide an important foundation for subsequent work by us and others on diverse cardiovascular problems ranging from understanding disease progression to designing improved interventions and devices.

Public Health Relevance

Cardiovascular disease remains the leading cause of death and disability among Americans. Many devastating complications of vascular disease progression (including atherosclerosis and aneurysms), compromised interventional procedures (including stents for treating atherosclerosis and coils for treating aneurysms), and failures of implanted cardiovascular devices (including heart valves and ventricular assist devices) result directly from intraluminal blood clots. Because the structural integrity of the clot is fundamental to its role in most of these complications, there is a need to understand better the underlying biomechanics. We will develop a novel in vivo clot model and be the first to quantify clot composition, structure, and mechanical properties as a function of its time of development. We submit that such quantification will be fundamental to many basic science and industrial studies seeking to improve vascular health.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Small Research Grants (R03)
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Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
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Peng, Grace
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Yale University
Engineering (All Types)
Schools of Engineering
New Haven
United States
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Lee, Y-U; Lee, A Y; Humphrey, J D et al. (2015) Histological and biomechanical changes in a mouse model of venous thrombus remodeling. Biorheology 52:235-45
Humphrey, J D; Holzapfel, G A (2012) Mechanics, mechanobiology, and modeling of human abdominal aorta and aneurysms. J Biomech 45:805-14
Karsaj, I; Humphrey, J D (2009) A mathematical model of evolving mechanical properties of intraluminal thrombus. Biorheology 46:509-27