A model describing the primary relations between the cardiac muscle and coronary circulation might be useful for interpreting coronary hemodynamics in case multiple types of coronary circulatory disease are present. The main contribution of the present study is the coupling of a microstructure-based heart contraction model with a 1D wave propagation model. The 1D representation of the vessels enables patient-specific modeling of the arteries and/or can serve as boundary conditions for detailed 3D models, while the heart model enables the simulation of cardiac disease, with physiology-based parameter changes. Here, the different components of the model are explained and the ability of the model to describe coronary hemodynamics in health and disease is evaluated. Two disease types are modeled: coronary epicardial stenoses and left ventricular hypertrophy with an aortic valve stenosis. In all simulations (healthy and diseased), the dynamics of pressure and flow qualitatively agreed with observations described in literature. We conclude that the model adequately can predict coronary hemodynamics in both normal and diseased state based on patient-specific clinical data.

Constitutive models describing the arterial mechanical behavior are important in the development of catheterization products, to be used in arteries with a specific radius. To prove the possible existence of a constitutive model that, provided with a generic set of material and geometric parameters, is able to predict the radius-specific mechanical behavior of a coronary artery, the passive pressure-inner radius (P-r ( i )) and pressure-axial force change (P-ΔF ( z )) relations of seven porcine left anterior descending coronary arteries were measured in an in-vitro set-up and fitted with the model of Driessen et al. in J Biomech Eng 127(3):494-503 (2005), Biomech Model Mechanobiol 7(2):93-103 (2008). Additionally, the collagen volume fraction, physiological axial pre-stretch, and wall thickness to inner radius ratio at physiological loading were determined for each artery. From this, two generic parameter sets, each comprising four material and three geometric parameters, were obtained. These generic sets were used to compute the deformation of each tested artery using a single radius measurement at physiological loading as an artery-specific input. Artery-specific P-r ( i ) and P-ΔF ( z ) relations were predicted with an accuracy of 32 μm (2.3%) and 6 mN (29% relative to ΔF ( z )-range) on average compared to the relations measured in-vitro. It was concluded that the constitutive model provided with the generic parameters found in this study can well predict artery-specific mechanical behavior.

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 (β phys ). β phys , 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. β phys 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.

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In order to explain the disappearance of depot fat in rats fed on a diet containing 50% by weight of extremely hydrogenated vegetable fat, experiments were performed in which the diet inhibiting lipogenesis was enriched with biotin. Biotin was effective in maintaining normal adipose tissue stores. The dermal essential fatty acid deficiency syndrome which occurred in this dietary group was prevented by the administration of linoleic acid. Cecal contents of rats kept on diets with hydrogenated fat were analyzed for biotin concentration and showed depressed intestinal synthesis of this vitamin by the bacterial flora. These data suggest that the inhibited lipogenesis in animals fed extremely saturated fat is the result of essential fatty acid deficiency and thereby of a reduced synthesis (and increased utilization) of biotin required as coenzyme of fatty acid synthesis in the nonmitochondrial system of lipogenesis.

Fifty-two patients and 36 controls were compared in a search for insulin gene variants among type II diabetic patients with fasting hyperinsulinemia (above 90 microU/ml) and a fasting C-peptide to insulin molar ratio between 1.11 and 1.50. Alpha and beta alleles of the insulin gene were characterized by restriction analysis of polymerase chain reaction (PCR) products and direct sequencing. The more frequent occurrence of the alpha allele of the insulin gene within the control population as compared with a prevalence of the beta allele in the diabetic patients (P, 0.05) was observed. The beta allele, usually described as the rare allele, seems to be associated with the disease.

Measurement of coronary pressure and absolute flow dynamics have shown great potential in discerning different types of coronary circulatory disease. In the present study, the feasibility of assessing pressure and flow dynamics with a combination of two thermal methods, developed in combination with a pressure-sensor-tipped guide wire, was evaluated in an in vitro coronary model. A continuous infusion thermodilution method was employed to determine the average flow, whereas a thermal anemometric method was utilized to assess the pressure and flow dynamics, simultaneously. In the latter method, the electrical power supplied to an element, kept at constant temperature above ambient temperature, was used as a measure for the shear rate. It was found that, using a single calibration function, the method was able to assess coronary pressure and flow dynamics for different flow amplitudes, heart rates, and different pressure wires. However, due to the fact that the thermal anemometric method cannot detect local shear rate reversal, the method was unable to reliably measure flow dynamics close to zero. Nevertheless, the combined methodology was able to reliably assess diastolic hemodynamics. The diastolic peak flow and average diastolic resistance could be determined with a small relative error of (8 ± 7)% and (7 ± 5)%, respectively.