ISOLATED HEART PERFUSION WITH PERFLUORCHEMICAL EMULSION

这项工作的长期目标是确定 用作心脏灌流液的全氟化学乳剂 临床用途。我们之前已经证明，血液动力学， 离体鼠工作心脏的机械和能量功能更多 在较长的时间内稳定，当心脏充满了 全氟化学乳剂(Fluosol-43)与其灌流时相比 结晶Krebs-Henseleit碳酸氢盐缓冲液。我们现在提议进行实验 研制和鉴定从...分离的全心工作制剂 使用Fluosol-43作为灌流液的大型动物(兔子、羔羊、猪)。 经氟溶胶灌流心脏的血流动力学和能量功能 与之相比，心脏充满了 红细胞-白蛋白-Krebs-Henseleit溶液。生化特性 大鼠心脏和大心脏的准备工作将包括分析 底物利用(葡萄糖、乳酸、油酸盐、醋酸酯)及其研究 亚细胞活动(线粒体呼吸、肌原纤维ATPase、 肌浆网钙摄取，肌膜慢内向钙通道 转运、钾丢失)。大鼠心脏灌流 使用Krebs-Henseleit或胶体对照溶液将 有助于建立氟唑醇的防腐作用机制 离体心(氧气输送增加？肿胀压力增加？)。 在以后的实验中，我们将研究Fluosol-43灌流的功能 在缺血或缺氧条件下的离休工作心脏。 兔、羊离体心工作制剂的研制 猪将允许研究血液动力学、生理学和新陈代谢。 这些心脏在受控的生化和机械条件下。 这些制剂将会有广泛的应用，特别是在药物研究中。 胎儿和新生儿的心脏发育以及动物 在解剖和功能上与人类心脏相似的心脏是 需要的。我们的实验还将有助于建立亚细胞 促进离体心功能改善的机制(S) 全氟化学乳剂灌流及其作用机制(S) 全氟化学乳剂对缺血心脏可能的有益作用。

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.