Abstract
At a time of growing concern over the ethics of animal experimentation, mouse models are still an indispensable source of insight into the cardiovascular system and its most frequent pathologies. Nevertheless, reference data on the murine cardiovascular anatomy and physiology are lacking. In this work, we developed and validated an in silico, one dimensional model of the murine systemic arterial tree consisting of 85 arterial segments. Detailed aortic dimensions were obtained in vivo from contrast-enhanced micro-computed tomography in 3 male, C57BL/6J anesthetized mice and 3 male ApoE(-/-) mice, all 12-weeks old. Physiological input data were gathered from a wide range of literature data. The integrated form of the Navier-Stokes equations was solved numerically to yield pressures and flows throughout the arterial network. The resulting model predictions have been validated against invasive pressure waveforms and non-invasive velocity and diameter waveforms that were measured in vivo on an independent set of 47 mice. In conclusion, we present a validated one-dimensional model of the anesthetized murine cardiovascular system that can serve as a versatile tool in the field of preclinical cardiovascular research.
Highlights
Cardiovascular disease is often studied in a preclinical setting since small animal models offer more flexibility, easier access to in and ex vivo tissues, and faster disease progression than humans
3.1 General physiological parameters Main hemodynamic parameters estimated from the 1D model are presented in Table 3, along with values of the 3D model published by Cuomo et al (2015)
The original 1D model of the human systemic arterial tree that formed the basis of this work was developed (Stergiopulos et al, 1992) and improved (Reymond et al, 2009) in our lab, and has been successfully used as a research tool in a number of subsequent studies (Vardoulis et al, 2011, 2012)
Summary
Cardiovascular disease is often studied in a preclinical setting since small animal models offer more flexibility, easier access to in and ex vivo tissues, and faster disease progression than humans. In-depth research on aortic anatomy and physiology is not straightforward since, both in humans and mice, (non-)invasive measurements are (i) technically difficult to obtain, (ii) limited to a restricted number of aortic locations, and (iii) need to be justified from an ethical perspective. The development of a wide range of 1D models of the human arterial circulation (Avolio, 1980; Bessems et al, 2007; Mynard and Smolich, 2015; Sherwin et al, 2003; Stergiopulos et al, 1992; Wemple and Mockros, 1972) has allowed researchers to study the effect of alterations in anatomy or physiology (Vardoulis et al, 2011) without the ethical and technical limitations of in vivo measurements. To the best of our knowledge, the most complete computational model of the murine arterial tree is the FSI model of Cuomo et al (2015)
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