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.
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