ISOLATED HEART PERFUSION WITH PERFLUOROCHEMICAL EMULSION

我们的长期目标是建立最佳的成分 全氟化学(PFC)乳剂介质，用作02输送 体内和体外的药物。在拟议的研究中，我们将 比较两种药物对心脏生理生化的影响 APF-140E(一种由以下组成的新型实验乳液 全氟十氢萘与无营养脂肪酸乳化和 磷脂)，氟溶胶-43(全氟三丁胺的乳剂 Pluronic F-68)和生理介质(血液或红血 基于细胞的灌流液)。我们预计APF-140E将优于 目前可用的PFC乳剂的原因是：(A)其乳化剂是 生物脂混合物而不是合成表面活性剂，(B)其 在以下方面，PFC的生物保留时间比PFC短 目前的乳剂配方，以及(C)它可以用 高比例的全氟十氢林，这表明它会 有效地提供02和低Fi02。物理化学 APF-140E的性能也优于现行的 乳液；值得注意的是，它在室温或 冰箱温度低，粘度低。 一种分离的工作兔心脏准备将用于研究 PFC介质组分的心脏效应。 孤立者的生理功能、稳定性和寿命 心脏将被评估，两人之间的关系也将被评估 生理功能和亚细胞过程，包括过量 钙蓄积、膜脂过氧化、体液过剩 积累，以及净ATP和磷酸肌酸的利用。 体外循环后心脏亚结构的完整性和生理功能 活体暴露于PFC和对照介质也将被确定 这项工作将导致新的合成02- 携带将有助于(A)增强O2交付的解决方案 对缺血器官，(B)增强02的递送 带血管的肿瘤以提高放射治疗的疗效， (C)一般输血用途；及(D)器官的体外支持。 这样的解决方案将是当前液体和血液的宝贵补充 替代疗法，并将提供新的疗法 脑血管和心脏疾病以及癌症的类型。

Our long-range objective is to establish optimum compositions of perfluorochemical (PFC) emulsion media for use as 02 delivery agents in vivo and in vitro. In the proposed research, we will compare the cardiac physiological and biochemical effects of APF-140E (a novel experimental emulsion composed of perfluorodecalin emulsified with nutrient free fatty acids and phospholipids), Fluosol-43 (an emulsion of perfluorotributylamine in Pluronic F-68), and physiological media (blood or a red blood cell-based perfusate). We expect APF-140E to be superior to currently-available PFC emulsions becuase: (a) its emulsifier is a biological lipid blend rather than a synthetic surfactant, (b) its PFC has a shorter biological retention time than the PFCs in current emulsion formulations, and (c) it can be formulated with high percentages of perfluorodecalin, which suggests that it will effectively deliver 02 and low Fi02. The physicochemical properties of APF-140E are also superior to those of current emulsions; notably, it is stable for long periods at room or refrigerator temperatures and has low viscosity. An isolated working rabbit heart prepartion will be used to study the cardiac effects of components of the PFC media. Physiological function, stability, and longevity of the isolated hearts will be assessed, as will the relationship between physiological function and subcellular processes including excess calcium accumulation, membrane lipid peroxidation, excess fluid accumulation, and net ATP and phosphocreatine utilization. Cardiac substructural integrity and physiological function after in vivo exposure to PFC and control media will also be determined This work will lead to the development of new synthetic 02- carrying solutions that will be useful for (a) enhancing 02 delivery to ischemic organs, (b) enhancing 02 delivery to poorly vascularized tumors to increase the efficacy of radiation therapy, (c) general transfusion use, and (d) in vitro support of organs. Such solutions will be a valuable adjunct to current fluid and blood replacement therapies and will offer new therapies for certain types of cerebrovascular and cardiac diseases and cancer.