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

医学界和科学界的大量经验数据表明，受到轻度热应激的细胞会过度表达热休克蛋白(HSP)，热休克蛋白对受损的细胞和组织具有保护和修复作用。我们已经完成了对热刺激条件的大量定量测量，这些条件对细胞培养中热休克蛋白的表达是最佳的。这项提案提出了一套独特的实验，旨在通过建立一种新的方案来生产和测量整个器官模型中的HSP表达，从而将这项技术带入下一阶段的开发。这些实验是基于我们医学院的一位同事开发并使用了20多年的现有灌流工作大鼠心脏模型。用微波源进行辐射将产生热应力，这非常适合于适应灌流装置，并在整个大鼠心脏产生均匀的能量吸收场。整个器官研究的第一个方面的重点是确定测量大鼠心脏中HSP产生的有效性，并将灌流试验的持续时间延长到尽可能长的时间。我们将实施新的测量技术，通过多平面磁共振温度成像(MRTI)来量化心脏的时间热场。虽然我们的实验室在生物热传递研究方面有几十年的经验，但这个项目是进入一个全新的研究领域的初步尝试，据我们所知，世界上任何地方都没有现有的经验。分子生物学领域的最新发展使这项工作成为可能，该项目在医学应用中具有巨大的潜在最终回报。该奖项由化学和运输系统部门的热运输和热加工项目资助。

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.