ISOLATED HEART PERFUSION WITH PERFLUOROCHEMICAL EMULSION

使用全氟化学乳液进行离体心脏灌注

• 批准号: 2216567
• 负责人: LEIGH DENISE SEGEL
• 金额: $ 21.26万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2216567
• 关键词: aminoacid metabolism; biomaterial evaluation; blood flow measurement; cryopreservation; fluosol; glucose metabolism; glutamates; heart function; heart metabolism; heart pharmacology; heart preservation; heart transplantation; induced hypothermia; isolation perfusion; laboratory rabbit; laboratory rat; nonhuman therapy evaluation; oxygen transport; phenanthrene; phospholipids; pyruvates; sheep; telemetry

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.

这项研究的长期目标是确定 和生物相容性的生理机制 含氟化合物乳剂。 这项工作涉及建立 含氟化合物乳液作为临床氧气输送剂的功效 以及涉及心脏和其他器官灌注的研究用途， 再灌注和保存。拟议的研究是 APE-LM低温保存心脏的研究 鸡蛋中由全氟全氢菲组成的氟化物乳液 蛋黄磷脂APE-LM乳剂具有特异性的心脏保护作用， 对保存哺乳动物（大鼠和兔）心脏的作用， 至少12-24小时，生理功能100%恢复。具体 拟议工作的目的是：（a）确定 维持心肌完整性并提供改善的心脏恢复 使用APE-LM延长低温心脏保存时间后的功能， 和（B）实现心脏功能的完全恢复， 绵羊保存心脏原位移植后存活情况 用含有APE-LM的培养基。在建议的资助期内， 机制负责基板的偏好和随之而来的影响， 将研究低温静止心脏中的能量产生。 保存介质中O2含量和输送量在确定 将研究保存期间心肌基质的使用模式。 将进行绵羊心脏原位移植，以量化心脏 功能和局部心肌血流量移植后（0小时至 30天），并确定接受 APE-LM保存的心脏移植。基因相同的绵羊将 用于捐赠者和接受者配对，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 产生关于以下方面的基本信息：（a）氟化合物 具有生物系统的乳液，其应用于以下领域 红细胞替代物和通常的脂质包封物质，和（B） 负责维持心脏完整性的机制 低温保存和改善心脏恢复的策略 短期和长期保存和再灌注。的疗效和安全性 用于心脏保存和体内 输血使用是该项目的健康相关目标。