An efficient finite difference model of blood flow through the coronary vessels is developed and applied to a geometric model of the largest six generations of the coronary arterial network. By constraining the form of the velocity profile across the vessel radius, the three-dimensional Navier-Stokes equations are reduced to one-dimensional equations governing conservation of mass and momentum. These equations are coupled to a pressure-radius relationship characterizing the elasticity of the vessel wall to describe the transient blood flow through a vessel segment. The two step Lax-Wendroff finite difference method is used to numerically solve these equations. The flow through bifurcations, where three vessel segments join, is governed by the equations of conservation of mass and momentum. The solution to these simultaneous equations is calculated using the multidimensional Newton-Raphson method. Simulations of blood flow through a geometric model of the coronary network are presented demonstrating physiologically realistic flow rates, washout curves, and pressure distributions.

An automatic segmentation technique has been developed and applied to two renal micro-computer tomography (CT) images. With the use of a 20-microm voxel resolution image, the arterial and venous trees were segmented for the rat renal vasculature, distinguishing resolving vessels down to 30 microm in radius. A higher resolution 4-microm voxel image of a renal vascular subtree, with vessel radial values down to 10 microm, was segmented. Strahler ordering was applied to each subtree using an iterative scheme developed to integrate information from the two segmented models to reconstruct the complete topology of the entire vascular tree. An error analysis of the assigned orders quantified the robustness of the ordering process for the full model. Radial, length, and connectivity data of the complete arterial and venous trees are reported by order. Substantial parallelism is observed between individual arteries and veins, and the ratio of parallel vessel radii is quantified via a power law. A strong correlation with Murray's Law was established, providing convincing evidence of the "minimum work" hypothesis. Results were compared with theoretical branch angle formulations, based on the principles of "minimum shear force," were inconclusive. Three-dimensional reconstructions of renal vascular trees collected are made freely available for further investigation into renal physiology and modeling studies.

The determinants of relaxation in cardiac muscle are poorly understood, yet compromised relaxation accompanies various pathologies and impaired pump function. In this study, we develop a model of active contraction to elucidate the relative importance of the [Ca2+]i transient magnitude, the unbinding of Ca2+ from troponin C (TnC), and the length-dependence of tension and Ca2+ sensitivity on relaxation. Using the framework proposed by one of our researchers, we extensively reviewed experimental literature, to quantitatively characterize the binding of Ca2+ to TnC, the kinetics of tropomyosin, the availability of binding sites, and the kinetics of crossbridge binding after perturbations in sarcomere length. Model parameters were determined from multiple experimental results and modalities (skinned and intact preparations) and model results were validated against data from length step, caged Ca2+, isometric twitches, and the half-time to relaxation with increasing sarcomere length experiments. A factorial analysis found that the [Ca2+]i transient and the unbinding of Ca2+ from TnC were the primary determinants of relaxation, with a fivefold greater effect than that of length-dependent maximum tension and twice the effect of tension-dependent binding of Ca2+ to TnC and length-dependent Ca2+ sensitivity. The affects of the [Ca2+]i transient and the unbinding rate of Ca2+ from TnC were tightly coupled with the effect of increasing either factor, depending on the reference [Ca2+]i transient and unbinding rate.

In individuals with effective Frank-Starling mechanism, the length dependence of tension facilitates the homogenization of stress and strain. This can result in synchronous contraction despite asynchronous electrical activation. In these individuals, synchronizing electrical activation through CRT may have minimal benefit.