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: 3341130
• 负责人: LEIGH DENISE SEGEL
• 金额: $ 18.21万
• 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 1994-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3341130
• 关键词: albumins; antioxidants; blood /plasma substitute; colloids; electrolyte balance; emulsions; flow cytometry; fluosol; heart circulation; heart function; heart metabolism; heart preservation; heart transplantation; isolation perfusion; laboratory rabbit; laboratory rat; organ culture; oxygen transport; phenanthrene; transplantation immunology

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.

我们的目标是确定 有效性和生物相容性的潜在机制， 含氟化合物乳液。 建议的工作继续我们的调查 APE-LM是一种新的长期低温心脏保存方法， 全氟全氢菲蛋乳剂 蛋黄磷脂 我们已经发现APE-LM发挥一种特异性的 保存哺乳动物（大鼠和兔）心脏的心脏保护作用 持续至少12-24小时，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)定量APE-LM保存的大鼠和兔心脏的恢复 在它们被移植并在体内再灌注之后。 我们推测 APE-LM的作用是通过其新的配方介导的，主要是通过 提供更高的O2含量、脂质乳化剂和上级物理性能 特性（小乳液粒径，低粘度）。 我们将 确定如何保存时，组件的影响， 保存介质是变化的，当介质的O2含量变化时， 以及当输送到心脏的O2变化时。 我们将决定如何 心脏膜的完整性和保存后的功能受到 蛋黄的成分，特别是胆固醇含量， 磷脂乳化剂 离体大鼠和家兔工作心脏 准备将用于量化收缩，输出，工作，流量， 新鲜的，保存的， 和移植后的心脏 此外，各种生物化学和 心肌膜完整性，氧合， 线粒体功能和能量供应/利用将被测量， 提示可逆性与不可逆性心肌梗死的可能机制 损伤，并获得一个实用的指数，心肌活力在 保存设置。 拟议的实验是针对 大型哺乳动物心脏的保存和移植 含氟化合物乳液。 我们的研究也是为了 关于（a）氟化合物与 具有广泛应用的生物系统乳液 红细胞替代品和脂质包封物质领域， 一般，和（B）改善心脏的机制和策略 保存和再灌注后恢复。