SGER: Development of a Perfused Heart Model for Heat Shock Protein Preconditioning

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Extensive empirical data within the medical and scientific communities indicate that cells subjected to mild thermal stress will over-express heat shock proteins (HSP), which are known to have protective and reparative effects on injured cells and tissues. We have completed extensive quantitative measurements of the thermal stimulation conditions optimal to HSP expression in cell cultures. This proposal presents a unique set of experiments designed to take this technology to the next level of development by establishing a new protocol for producing and measuring HSP expression in a whole organ model. The experiments are based on an existing perfused working rat heart model developed and used by one of our medical school colleagues for more than two decades. Thermal stress will be produced by irradiation with a microwave source, which is well suited for adaptation to the perfusion rig and to producing a uniform energy absorption field throughout a rat heart. The focus of this first aspect of the whole organ study is to determine the effectiveness of measuring HSP production in a rat heart and of extending the duration of the perfusion trial to as long a period as possible. We will implement novel measurement techniques to quantify the temporal thermal field, via multiplanar magnetic resonance temperature imaging (MRTI), in the heart. Although we have several decades of experience in bioheat transfer research in our laboratory, this project is the initial foray into a brand new domain of study in which there is no existing experience anywhere in the world (to our knowledge.) Recent developments in the field of molecular biology have made this work possible, and the project has a huge potential eventual payoff in medical applications. The award has been funded by the Thermal Transport and Thermal Processing Program of the Chemical and Transport Systems Division.