Pre-Clinical Investigational Systems to Evaluate Medical Technologies and Modulate Ex-Vivo Organ Function

Abstract

Objective/Background This thesis aims to develop and modify pre-clinical benchtop systems using real anatomy to aid in device testing. While many benchtop systems enable testing using artificial materials to mimic tissue, the systems within the Visible Heart® laboratories are focused on preserving explanted organs to enable more translational pre-clinical research. These systems continue to be modified to allow for a wider range of function to mimic different environments for device designers. This thesis provides summaries of anatomical models used in device design and organ preservation, characterizations of modulators of cardiac function on the Visible Heart® apparatus, and developments of systems to better preserve and evaluate functional lungs and kidneys ex vivo.

Methods Through the summaries of the anatomical models used with the Visible Heart® laboratories, researchers can better understand how real anatomies are useful when designing devices and therapies. The summary of the functional evaluations of kidneys, lungs, and hearts reviews the years of research that allows perfusion systems to continuously monitor ex vivo organs for functional changes and disease state replication.

The modification to the utilized perfusate on the Visible Heart® apparatus expands the use of this pre-clinical testbed to allow for the collection of data that more closely resembles data collected in vivo. The increased viscosity of the perfusate more closely mimics the blood moving through the heart and its various anatomic regions. This allows device designers to study more cardiac devices and therapies. The goal of evaluating the reanimated heart’s function was to compare the functional viability of the heart using both the traditional perfusate and the higher viscosity perfusate, giving researcher’s the most complete picture of the translational properties of their collected data. The ability to modulate ex vivo heart function using pharmacologic agents is central to understanding and expanding the capabilities of the Visible Heart® apparatus. Through this work, not only can researchers collect data in various functional states, but they can also predict how the heart will respond to a specified concentration of pharmacologic agent present v within the perfusate, and therefore induce a desired functional state during ex vivo perfusion. The development of a dilated cardiomyopathy ex vivo model allows researchers to perform investigations within an environment that cannot be achieved using pharmacologic responses i.e., anatomic changes. The dilated cardiomyopathy model achieves yet another environment that researchers may test within.

Years of studying and experience with the ex vivo heart perfusion guided the development of ex vivo perfusion systems for the lungs and kidneys. These two systems expand researchers’ environments to use real tissue coupled with increased access to the organs. The abilities to monitor functional parameters also allows researchers to collect the most translational data possible.

Conclusions This dissertation provides researchers with the knowledge about what anatomical model may serve their investigation best, expands testing environments which utilize ex vivo perfusion methods for hearts, and provides detailed designs and execution of perfusion systems for lungs and kidneys.