title: Aerobic preservation of organs using a new perflubron/lecithin emulsion stabilized by molecular dowels.
abstract: The purpose of the study reported here was to explore a new strategy for the aerobic preservation of transplants using stable concentrated fluorocarbon emulsions as an oxygen delivery system. Fluorocarbons (FCs) are synthetic molecules, chemically and biologically inert, with a high oxygen-dissolving capacity. As they do not mix with water, it is necessary to emulsify them for intra-vascular use. Perfluorooctyl bromide (or perflubron) can be emulsifled with egg-yolk phospholipid (EYP), a nontoxic emulsifiant. The recent adjunction of amphiphilic fluorocarbon-hydrocarbon diblock molecules allows the obtaining of stable emulsions. By contrast with hemoglobin, fluorocarbons release oxygen following Henry's linear law rather than Barcroft's sigmoid curve. Release of oxygen by the FCs is only slightly influenced by temperature, which is an advantage for the preservation of organs. We tested a new 90% w/v fluorocarbon stem emulsion (perflubron/EYL/F6H10) diluted to 36% w/v with a hydroelectrolytic solution containing albumin, on four multiple organ blocks (MOBs; heart-lungs, liver, pancreas, kidneys, small intestine) of rats (EMOBs). Five control MOBs were perfused with a 50% v/v mixture of rat-blood and Krebs solution (KBMOBs). The lungs were ventilated with a FiO2 = 100%. In all cases the survival of the MOBs was greater than 210 min, with stable hemodynamics and preserved hydroelectrolytic and acid-base balances. The levels of lactate, amylase, and CK of the EMOBs were inferior (P < 0.05) to those of the KBMOBs between the first and the second hour. The diuresis of the EMOBs was higher (P < 0.05) than that of the KBMOBs (5.65 +/- 1.76 vs 1.21 +/- 0.28 mg/min). The production of bile, and the AST and ALT levels, were not significantly different. The PaO2 of the EMOBs was higher (P < 0.01) than for the KBMOBs. In normothermy, the maintenance of an aerobic metabolism using the FC emulsion caused less damage to the organs. Aerobic preservation of organs using FC emulsions therefore appears to be an attractive alternative to the presently used cold ischemia.
authors.affiliation: Laboratoire de Recherches Chirurgicales, INSERM U 281, France.
authors.forename: E J
authors.initials: EJ
authors.lastname: Voiglio
authors.forename: L
authors.initials: L
authors.lastname: Zarif
authors.forename: F C
authors.initials: FC
authors.lastname: Gorry
authors.forename: M P
authors.initials: MP
authors.lastname: Krafft
authors.forename: J
authors.initials: J
authors.lastname: Margonari
authors.forename: X
authors.initials: X
authors.lastname: Martin
authors.forename: J
authors.initials: J
authors.lastname: Riess
authors.forename: J M
authors.initials: JM
authors.lastname: Dubernard
mesh_terms: D000818:Animals; D001769:Blood; D004355:Drug Stability; D004655:Emulsions; D005466:Fluorocarbons; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics; D006842:Hydrocarbons, Brominated; D007552:Isotonic Solutions; D008297:Male; D009926:Organ Preservation; D010713:Phosphatidylcholines; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004655:Emulsions; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D010713:Phosphatidylcholines; D005947:Glucose; C003072:perflubron