ISOLATED HEART PERFUSION WITH PERFLUOROCHEMICAL EMULSION

这项研究的长期目标是确定生化 以及药效和生物相容性的生理机制 含氟化学乳剂。这项工作涉及到建立 氟化乳剂作为氧气输送制剂的临床应用效果 以及涉及心脏和其他器官灌注的研究用途， 再灌流和保存。拟议的研究是以下研究的延续 新型APE-LM用于低温心脏保存的研究 鸡蛋中全氟过氢菲组成的荧光化学乳剂 蛋黄磷脂。APE-LM乳剂具有特殊的心脏保护作用 对哺乳动物(大鼠和兔)心脏的保存效果 至少12~24小时，生理功能100%恢复。具体的 拟议工作的目标是：(A)确定 保持心肌完整性，促进心脏恢复 使用APE-LM延长低温心脏保存时间后的功能 和(B)实现心功能的完全恢复和长期 绵羊保存心脏原位移植后的存活 在含有APE-LM的培养基上培养。在建议的授权期内， 底物偏好及由此产生的影响的机制 我们将研究低温静止心脏的能量产生。 保存液O2含量和输送在测定中的作用 将研究保存过程中心肌基质的使用模式。 将对绵羊心脏进行原位移植以量化心脏 移植后功能和局部心肌血流量(0小时至 30天)，并确定接种的绵羊的长期存活率 移植APE-LM保存的心脏。基因相同的绵羊会 用于捐赠者和接受者对，这将使我们能够量化 心功能并确定APE-LM保存的充分性 免疫抑制剂或排斥反应的并发症。这项研究将 提供关于以下方面的基本信息：(A)氟化学物质的相互作用 具有生物体系的乳剂，其在以下领域中有应用 一般的红细胞代用品和脂质包裹的物质，以及(B) 维持心脏完整性的机制 低温保存及提高心脏复苏率的策略 短期和长期保存和再灌流。有效率和安全性 用于心脏保存和活体保存的氟化学乳剂 输血用途是该项目与健康相关的目标。

The long-range objective of this research is to determine the biochemical and physiological mechanisms underlying the efficacy and biocompatibility of fluorochemical emulsions. This work is concerned with establishing the efficacy of fluorochemical emulsions as O2 delivery agents for clinical and investigational uses involving heart and other organ perfusion, reperfusion, and preservation. The proposed research is a continuation of studies on hypothermic heart preservation using APE-LM, a novel fluorochemical emulsion composed of perfluoroperhydrophenanthrene in egg yolk phospholipid. The APE-LM emulsion exerts a specific cardioprotective effect in preserving mammalian (rat and rabbit) hearts for periods up to at least 12-24 h with 100% recovery of physiologic function. The Specific Aims of the proposed work are: (a) to determine the mechanisms that maintain myocardial integrity and provide for improved recovery of cardiac function after extended hypothermic heart preservation times using APE-LM, and (b) to achieve complete recovery of cardiac function and long-term survival of sheep following orthotopic transplantation of hearts preserved with medium containing APE-LM. During the proposed grant period, the mechanisms responsible for substrate preferences and consequent effects on energy production in hypothermic quiescent hearts will be investigated. The role of preservation medium O2 content and delivery in determining myocardial substrate use patterns during preservation will be studied. Orthotopic transplants of sheep hearts will be done to quantify cardiac function and regional myocardial blood flow after transplant (0 hours to 30 days), and to determine long-term survival of sheep that receive transplants of APE-LM-preserved hearts. Genetically-identical sheep will be used for donor and recipient pairs which will allow us to quantify cardiac function and determine the adequacy of APE-LM preservation without the complications of immunosuppressants or rejection. This research will yield fundamental information on: (a) the interaction of fluorochemical emulsions with biological systems, which has application in the areas of red cell substitutes and lipid-encapsulated substances in general, and (b) mechanisms responsible for maintaining cardiac integrity during hypothermic preservation and strategies to improve cardiac recovery after short- and long-term preservation and reperfusion. The efficacy and safety of fluorochemical emulsions for heart preservation and for in vivo transfusion uses are health-related goals of this project.