Cn Chantal van den Broek

An Ex Vivo Platform to Simulate Cardiac Physiology: A New Dimension for Therapy Development and Assessment:

Purpose Cardiac research and development of therapies and devices is being done with in silico models, using computer simulations, in vitro models, for example using pulse duplicators or in vivo models using animal models. These platforms, however, still show essential gaps in the study of comprehensive cardiac mechanics, hemodynamics, and device interaction. The PhysioHeart platform was developed to overcome these gaps by the ability to study cardiac hemodynamic functioning and device interaction ex vivo under in vivo conditions. Methods Slaughterhouse pig hearts (420 ± 30 g) were used for their morphological and physiological similarities to human hearts. Hearts were arrested, isolated and transported similar to transplantation protocols. After preparation, the hearts were connected to a special circulatory system that has been engineered using physical and medical principles. Through coronary reperfusion and controlled cardiac loading, physiological cardiac performance was achieved while hemodynamic parameters were continuously monitored. Results Normal cardiac hemodynamic performance was achieved both qualitatively, in terms of pulse waveforms, and quantitatively, in terms of average cardiac output (4 l/min) and pressures (110/75 mmHg). Cardiac performance was controlled and kept at normal levels for up to 4 hours, with only minor deterioration of hemodynamic performance. Conclusions With the PhysioHeart platform we were able to reproduce normal physiological cardiac conditions ex vivo. The platform enables us to study, under different but controlled physiological conditions, form, function, and device interaction through monitoring of performance parameters and intra-cardiac visualization. Although the platform has been used for pig hearts, application of the underlying physical and engineering principles to physiologically comparable hearts from different origin is rather straightforward.

The fiber orientation in the coronary arterial wall at physiological loading evaluated with a two-fiber constitutive model.

A patient-specific mechanical description of the coronary arterial wall is indispensable for individualized diagnosis and treatment of coronary artery disease. A way to determine the artery’s mechanical properties is to fit the parameters of a constitutive model to patient-specific experimental data. Clinical data, however, essentially lack information about the stress-free geometry of an artery, which is necessary for constitutive modeling. In previous research, it has been shown that a way to circumvent this problem is to impose extra modeling constraints on the parameter estimation procedure. In this study, we propose a new modeling constraint concerning the in-situ fiber orientation (βphys). βphys, which is a major contributor to the arterial stress–strain behavior, was determined for porcine and human coronary arteries using a mixed numerical–experimental method. The in-situ situation was mimicked using in-vitro experiments at a physiological axial pre-stretch, in which pressure–radius and pressure–axial force were measured. A single-layered, hyperelastic, thick-walled, two-fiber material model was accurately fitted to the experimental data, enabling the computation of stress, strain, and fiber orientation. βphys was found to be almost equal for all vessels measured (36.4 ± 0.3)°, which theoretically can be explained using netting analysis. In further research, this finding can be used as an extra modeling constraint in parameter estimation from clinical data.

Mechanical Characterization of Vascular Smooth Muscle

Remodeling of the arterial wall, in response to e.g. induced hypertension, vasoconstriction, and reduced cyclic stretch, has been studied in detail to get insight into vascular pathologies [1]. Constitutive models are helpful to the understanding of the relation between different processes that occur in the arterial wall during remodeling. Including the smooth muscle cell (SMC) behavior in constitutive models is relevant, as those cells may change tone when subjected to an altered mechanical loading and can initiate arterial remodeling.Copyright

Fiber Orientation in Porcine Coronaries, as Described by the Holzapfel Model, is Fixed at Physiological Loading

Insight into the mechanical properties of the coronary arterial wall can give valuable information concerning atherosclerosis, wall remodeling, and predicting the effects of medical intervention; e.g. balloon angioplasty [1,2]. Furthermore, knowledge of the mechanical properties of the arterial wall is important in modeling the coronary circulation and explaining its hemodynamical functioning.Copyright

A mixed experimental-numerical estimation strategy to characterize arterial wall properties including residual strains

To model materials mechanically, it is necessary to determine the parameters of the constitutive model which determine its mechanical behavior. To be able to do this correctly it is important to know the zero-stress state of the material.Copyright

What is the in vivo axial strain of a porcine coronary artery

Knowledge of mechanical properties of livingarteries is important to understand vascular functionduring health and disease. An effective way tostudy the behavior of living tissue is organ culture.In arterial culture the artery should be loaded at invivo levels to maintain the arterys viability. The invivo axial strain of coronary arteries, however, isunknown. Therefore, the aim of this study is todetermine the physiological axial strain of theporcine left anterior descending coronary artery(LAD). Based on Weizscker (1983) and Schulze-Bauer (2003) it was hypothesized that: The in vivoaxial strain of an artery is the strain at which theaxial force (Fax) is relatively insensitive to changesin pressure (P). This physiological strain (fig.1,right, red line) was determined in an organ culturemodel. To test the hypothesis an isolated beatingheart experiment, in which a porcine heart is loadedphysiologically, was performed. Due to thepumping of the heart, a cyclic axial strain isinduced to the coronaries.

THE MECHANICAL PROPERTIES OF PORCINE CORONARY ARTERIES DETERMINED WITH A MIXED EXPERIMENTAL-NUMERICAL APPROACH

Mechanical characterization of the coronary arterial wall is important for several reasons. Mechanical factors play an important role in the development of atherosclerosis [1]. Atherosclerotic coronary arteries may be treated mechanically with interventions like PTCA and stent implantation, 1265000 PTCA procedures were performed in the United States in 2005 [2]. Furthermore, knowledge of the mechanical properties of the arterial wall is important for modeling of the coronary circulation and explaining its hemodynamics.Copyright

Mechanical Properties of the Porcine Coronary Artery

Knowledge of mechanical properties of living arteries isimportant to understand vascular function during health, disease andintervention. A mechanical model of the vascular tree would facilitatethe development of (balloon-)catheters and stents.We have developed an ex vivo model in which a porcinecoronary artery can be kept at physiological circumstances; hencecoronary pressure and flow, cyclic longitudinal elongation of thesegment, physiological wall shear stresses, etc. are controlled, whileenabling measurement of its mechanical behavior. Arterial mechanicalbehavior was determined for segments of the porcine left anteriordescending coronary artery (LAD, fig. 1a) by simultaneousmeasurement of pressure (P), diameter (D) and axial force (Fax) duringdynamic loading at different axial strains. Also, the physiological axialstrain of the LAD was determined, based on the hypothesis that: Thein vivo axial strain of an artery is the strain at which the axial force isrelatively insensitive to changes in pressure [1,2], as shown in figure1b.