ISOLATED HEART PERFUSION WITH PERFLUORCHEMICAL EMULSION

使用全氟化学乳液进行离体心脏灌注

• 批准号: 3341126
• 负责人: LEIGH DENISE SEGEL
• 金额: $ 14.61万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1988-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341126
• 关键词: cell components; colloids; electrolyte balance; emulsions; heart; heart circulation; heart function; hemodynamics; isolation perfusion; myocardial ischemia /hypoxia; organ culture; osmotic pressure; tissue /organ preservation

The long-range objective of this work is to determine the suitability of perfluorochemical emulsions as cardiac perfusates for investigative and clinical purposes. We have previously shown that the hemodynamic, mechanical, and energetic functions of isolated working rat hearts are more stable over a prolonged time period when the hearts are perfused with a perfluorochemical emulsion (Fluosol-43) than when they are perfused with crystalloid Krebs-Henseleit bicarbonate buffer. We now propose experiments to develop and characterize isolated working whole heart preparations from large animals (rabbits, lambs, pigs) using Fluosol-43 as perfusate. Hemodynamic and energetic function of the Fluosol-perfused hearts will be compared with that of hearts perfused with an erythrocyte-albumin-Krebs-Henseleit solution. Biochemical characterization of the rat heart and large heart preparations will include analysis of substrate utilization (glucose, lactate, oleate, acetate) and study of subcellular activities (mitochondrial respiration, myofibrillar ATPase, sarcoplasmic reticulum Ca++ uptake, sarcolemma slow inward calcium channel transport, K+ loss) during Fluosol perfusion. Rat heart perfusions performed with Krebs-Henseleit or with a colloidal control solution will help establish the mechanism of Fluosol's preservative effect on the isolated heart (increased oxygen delivery? increased oncotic pressure?). In later experiments we will study the function of Fluosol-43-perfused isolated working hearts under ischemic or hypoxic conditions. The development of isolated working heart preparations from rabbits, lambs, and pigs will permit the study of hemodynamics, physiology, and metabolism of those hearts under controlled biochemical and mechanical conditions. These preparations will have wide application, particularly in studies of fetal and newborn heart development and in experiments in which animal hearts that are anatomically and functionally similar to human hearts are needed. Our experiments will also help establish the subcellular mechanism(s) that contribute to the improved function of isolated hearts perfused with perfluorochemical emulsion and the mechanism(s) of the putative beneficial effect of perfluorochemical emulsion on ischemic hearts.

这项工作的长期目标是确定 作为心脏灌注液的全氟化学品乳剂， 临床目的。 我们之前已经证明了血液动力学， 离体工作大鼠心脏的机械和能量功能更 当心脏灌注一种 全氟化学品乳液（Fluosol-43）比当它们灌注有 晶体Krebs-Henseleit碳酸氢盐缓冲液。 我们现在提出实验 开发和表征分离的工作全心脏制剂， 使用Fluosol-43作为灌注液的大型动物（兔、羔羊、猪）。 Fluosol灌注心脏的血流动力学和能量功能将 与心脏灌注的心脏相比， 红细胞-白蛋白-Krebs-Henseleit溶液。 生物化学表征 大鼠心脏和大心脏制备物的分析将包括 底物利用（葡萄糖、乳酸盐、油酸盐、乙酸盐）和 亚细胞活性（线粒体呼吸，肌原纤维ATP酶， 肌浆网Ca++摄取，肌膜慢内向钙通道 运输，K+损失）。 大鼠心脏灌注 使用Krebs-Henseleit或胶体对照溶液进行的检测将 有助于建立氟溶胶防腐作用的机理 离体心脏（增加氧气输送？ 压力增加？）。 在以后的实验中，我们将研究Fluosol-43-灌注的功能 在缺血或缺氧条件下的离体工作心脏。 家兔、羔羊、家兔、绵羊、 猪将允许研究血液动力学、生理学和新陈代谢 在受控的生物化学和机械条件下的心脏。 这些制剂将有广泛的应用，特别是在研究 胎儿和新生儿心脏发育以及在实验中， 在解剖学和功能上与人类心脏相似的心脏， needed. 我们的实验也将有助于建立亚细胞 有助于改善离体心脏功能的机制 灌注全氟化学乳液的机理和（S）的 全氟乳剂对缺血心脏的假定有益作用。