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: 3341128
• 负责人: LEIGH DENISE SEGEL
• 金额: $ 10.7万
• 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 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341128
• 关键词: albumins; antioxidants; blood /plasma substitute; chemical stability; colloids; electrolyte balance; emulsions; flow cytometry; fluorine; fluosol; heart; heart circulation; heart function; heart metabolism; heart preservation; hemodynamics; isolation perfusion; laboratory rabbit; membrane channels; organ culture; osmotic pressure

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.

我们的长期目标是建立最佳组合物， 用作O2输送的全氟化学品（PFC）乳剂介质 体内和体外的药剂。 在研究中，我们将 比较心脏的生理和生化作用， APF-140 E（一种新型实验乳剂，由 用营养游离脂肪酸乳化的全氟萘烷， 磷脂）、Fluosol-43（全氟三丁胺的乳液 Pluronic F-68中）和生理介质（血液或红血 基于细胞的灌注液）。 我们预计APF-140 E将优于上级 目前可用的PFC乳液，因为：（a）其乳化剂是 生物脂质共混物而不是合成表面活性剂，（B）其 全氟化碳的生物保留时间比全氟化碳短， 目前的乳液制剂，和（c）它可以配制成 高比例的全氟萘烷，这表明它将 有效地输送O2和低FiO 2。 理化 APF-140 E的性能也优于目前的上级 乳液;值得注意的是，它在室温或室温下长期稳定， 冰箱温度和粘度低。 本实验采用离体工作兔心， PFC培养基成分的心脏效应。 隔离的生理功能、稳定性和寿命 心，是一种境界，也是一种境界。 生理功能和亚细胞过程，包括过量 钙积累，膜脂过氧化，过量水 积累和净ATP和磷酸肌酸利用。 心脏亚结构完整性和生理功能 还将测定PFC和对照培养基的体内暴露量 这项工作将导致新的合成02- 携带将用于（a）增强O2输送的溶液 （B）增强O2递送至缺血器官， 血管化肿瘤以增加放射治疗的功效， (c)一般输血使用，以及（d）器官的体外支持。 这样的解决方案将是一个有价值的辅助目前的液体和血液 替代疗法，并将提供新的疗法， 心脑血管疾病和癌症。