ISOLATED HEART PERFUSION WITH PERFLUOROCHEMICAL EMULSION

我们的目标是确定生物化学和生理学 药效和生物相容性的潜在机制， 含氟化学乳剂。拟议的工作将继续我们的调查 新型APE-LM在心脏长期低温保存中的应用 鸡蛋中全氟过氢菲组成的荧光化学乳剂 蛋黄磷脂。我们已经发现APE-LM发挥了特定的作用 哺乳动物(大鼠和兔)心脏保存的心脏保护作用 在至少12-24小时内100%恢复生理 功能。拟议工作的具体目标是：(A)确定 APE-LM发挥这种意想不到的有益作用的机制，以及 (B)量化APE-LM保存的大鼠和兔心脏的回收率 在体内移植和再灌流后。我们假定 APE-LM的作用主要是通过其新剂型介导的 提供更高的02含量、脂肪乳化剂和优异的物理性能 性能(乳化液颗粒小、粘度低)。我们会 确定当组件的 保存介质是不同的，当介质中的O2含量变化时， 而当02递送到心脏时则是多种多样的。我们将决定如何 心肌膜完整性和保存后功能受以下因素影响 蛋黄的成分，尤指蛋黄的胆固醇含量 磷脂乳化剂。离体工作大鼠和兔心 准备工作将用于量化收缩、产出、做功、流动、 新鲜的，腌制的，新鲜的， 以及移植后的心脏。此外，各种生化和 心肌膜完整性、氧合、 线粒体功能和能量供应/利用将被测量到 提示可逆性和不可逆性心肌的可能机制 并获得一个实用的心肌存活指数。 保存设置。拟议中的实验旨在 大型哺乳动物心脏的保存与移植 含氟化学乳剂。我们的研究也旨在产生 关于(A)氟化学物质相互作用的基本信息 具有生物体系的乳状液，具有广泛的应用前景 中国红血球代用品和脂质包膜物质的面积 (B)改善心脏疾病的机制和策略 保存再灌流后恢复正常。

Our objective is to determine the biochemical and physiological mechanisms underlying the efficacy and biocompatibility, of fluorochemical emulsions. The proposed work continues our investigation of long-term hypothermic cardiac preservation using APE-LM, a novel fluorochemical emulsion composed of perfluoroperhydrophenanthrene in egg yolk phospholipid. We have found that APE-LM exerts a specific cardioprotective effect in preserving mammalian (rat and rabbit) hearts for periods of at least 12-24 hr with 100% recovery of physiological function. The specific aims of the proposed work are to (a) determine the mechanism by which APE-LM exerts this unexpected salutary effect, and (b) to quantify the recovery of APE-LM-preserved rat and rabbit hearts after they are transplanted and reperfused in vivo. We postulate that APE-LM's effect is mediated by its novel formulation primarily by providing a higher 02 content, a lipid emulsifier, and superior physical properties (small emulsion particle size, low viscosity). We will determine how preservation is affected when components of the preservation medium are varied, when 02 content of the medium is varied, and when 02 delivery to the heart is varied. We will determine how cardiac membrane integrity and post-preservation function are affected by the composition, particularly the cholesterol content, of the egg yolk phospholipid emulsifier. Isolated working rat and rabbit heart preparations will be used to quantify contractile, output, work, flow, energetic, metabolic, and structural characteristics of fresh, preserved, and post-transplant hearts. In addition, various biochemical-and physiological indices of myocardial membrane integrity, oxygenation, mitochondrial function, and energy supply/utilization will be measured to suggest possible mechanisms of reversible vs. irreversible myocardial damage and to obtain a practical index of myocardial viability in the preservation setting. The proposed experiments are directed toward preservation and transplantation of large mammalian hearts using fluorochemical emulsions. Our research is also designed to yield fundamental information on (a) the interaction of fluorochemical emulsions with biological systems, which has application in the broad areas of red cell substitutes and lipid-encapsulated substances in general, and (b) the mechanisms and strategies to improve cardiac recovery after preservation and reperfusion.