A Study of the Dynamics of Cardiac Ischemia using Experimental and Modeling Approaches

The dynamics of cardiac ischemia was investigated using experimental studies and computer simulations. An experimental model consisting of an isolated and perfused canine heart with full control over blood flow rate to a targeted coronary artery was used in the experimental study and a realistically shaped computer model of a canine heart, incorporating anisotropic conductivity and realistic fiber orientation, was used in the simulation study. The phenomena investigated were: (1) the influence of fiber rotation on the epicardial potentials during ischemia and (2) the effect of conductivity changes during a period of sustained ischemia. Comparison of preliminary experimental and computer simulation results suggest that as the ischemic region grows from the endocardium towards the epicardium, the epicardial potential patterns follow the rotating fiber orientation in the myocardium. Secondly, in the experimental studies it was observed that prolonged ischemia caused a subsequent reduction in the magnitude of epicardial potentials. Similar results were obtained from the computer model when the conductivity of the tissue in the ischemic region was reduce

Optimization of MicroCT Imaging and Blood Vessel Diameter Quantitation of Preclinical Specimen Vasculature with Radiopaque Polymer Injection Medium

Vascular networks within a living organism are complex, multi-dimensional, and challenging to image capture. Radio-angiographic studies in live animals require a high level of infrastructure and technical investment in order to administer costly perfusion mediums whose signals metabolize and degrade relatively rapidly, diminishing within a few hours or days. Additionally, live animal specimens must not be subject to long duration scans, which can cause high levels of radiation exposure to the specimen, limiting the quality of images that can be captured. Lastly, despite technological advances in live-animal specimen imaging, it is quite difficult to minimize or prevent movement of a live animal, which can cause motion artifacts in the final data output. It is demonstrated here that through the use of postmortem perfusion protocols of radiopaque silicone polymer mediums and ex-vivo organ harvest, it is possible to acquire a high level of vascular signal in preclinical specimens through the use of micro-computed tomographic (microCT) imaging. Additionally, utilizing high-order rendering algorithms, it is possible to further derive vessel morphometrics for qualitative and quantitative analysis

Effect of Nonuniform Interstitial Space Properties on Impulse Propagation: A Discrete Multidomain Model

This work presents a discrete multidomain model that describes ionic diffusion pathways between connected cells and within the interstitium. Unlike classical models of impulse propagation, the intracellular and extracellular spaces are represented as spatially distinct volumes with dynamic/static boundary conditions that electrically couple neighboring spaces. The model is used to investigate the impact of nonuniform geometrical and electrical properties of the interstitial space surrounding a fiber on conduction velocity and action potential waveshape. Comparison of the multidomain and bidomain models shows that although the conduction velocity is relatively insensitive to cases that confine 50% of the membrane surface by narrow extracellular depths (≥2 nm), the action potential morphology varies greatly around the fiber perimeter, resulting in changes in the magnitude of extracellular potential in the tight spaces. Results also show that when the conductivity of the tight spaces is sufficiently reduced, the membrane adjacent to the tight space is eliminated from participating in propagation, and the conduction velocity increases. Owing to its ability to describe the spatial discontinuity of cardiac microstructure, the discrete multidomain can be used to determine appropriate tissue properties for use in classical macroscopic models such as the bidomain during normal and pathophysiological conditions