ISOLATED HEART PERFUSION WITH PERFLUORCHEMICAL EMULSION

这项工作的长期目标是确定 全氟化合物乳液作为心脏灌注液用于研究和 临床目的。 我们之前已经表明，血流动力学， 离体工作大鼠心脏的机械和能量功能更多 当心脏灌注有 全氟化合物乳液（Fluosol-43）比灌注时要好 晶体 Krebs-Henseleit 碳酸氢盐缓冲液。 我们现在提出实验 开发和表征隔离工作全心准备 使用 Fluosol-43 作为灌注液的大型动物（兔子、羔羊、猪）。 Fluosol 灌注心脏的血流动力学和能量功能将 与灌注有 红细胞-白蛋白-Krebs-Henseleit 溶液。 生化表征 大鼠心脏和大心脏制剂的分析将包括 底物利用（葡萄糖、乳酸盐、油酸盐、乙酸盐）和研究 亚细胞活动（线粒体呼吸、肌原纤维 ATP 酶、 肌浆网钙摄取，肌膜缓慢向内钙通道 Fluosol 灌注期间的运输、K 损失）。 大鼠心脏灌注 用 Krebs-Henseleit 或胶体对照溶液进行 帮助建立Fluosol的防腐作用机制 离体心脏（增加氧气输送？增加胶体渗透压？）。 在后面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分离工作心脏。 兔、羔羊离体工作心脏制剂的开发 猪将允许研究血流动力学、生理学和新陈代谢 这些心脏在受控的生化和机械条件下。 这些制剂将具有广泛的应用，特别是在研究 胎儿和新生儿心脏发育以及动物实验 解剖学和功能上与人类心脏相似的心脏是 需要。 我们的实验还将有助于建立亚细胞 有助于改善离体心脏功能的机制 全氟化学乳液灌注及其机理 全氟化学乳剂对缺血心脏的假定有益作用。

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.