title: Dose-dependent reduction of myocardial infarct size with the perfluorochemical Fluosol-DA.
abstract: The perfluorochemical Fluosol-DA has been shown to reduce infarct size. However, the dose-response relationship of the agent is unknown. Because perfluorochemicals (PFC) can potentially saturate the reticuloendothelial system and decrease carbon clearance as well as cause a transient elevation in liver enzymes, the present study was conducted to determine the lowest effective dose. New Zealand White rabbits (n = 73) were randomly selected prior to infarction to receive 10, 15, 20, 25, or 30 ml/kg PFC or an equivalent volume of 5% dextran (control) intravenously. Animals underwent 30 minutes of coronary artery occlusion with PFC or dextran infused over a 30-minute period starting at 20 minutes into the occlusion. Animals were put to death at 24 hours and infarct size was determined histologically and quantitated by computerized planimetry. Neutrophil infiltration into the ischemic myocardium was evaluated semiquantitatively. No hemodynamic differences were noted within groups. Infarct size was similar to that of controls in animals treated with 10 or 15 ml/kg PFC. Significant infarct size reduction, however, was noted in animals treated with 20, 25, and 30 ml/kg PFC versus controls; (p = 0.05, 0.04, and 0.02, respectively). Maximal infarct size reduction was seen with 30 ml/kg PFC (35%). Neutrophil infiltration was significantly decreased in all groups treated with PFC. These results show that intravenous Fluosol-DA significantly reduces infarct size at a minimal dose of 20 ml/kg.
authors.affiliation: Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000.
authors.forename: H E
authors.initials: HE
authors.lastname: Rice
authors.forename: R
authors.initials: R
authors.lastname: Virmani
authors.forename: C L
authors.initials: CL
authors.lastname: Hart
authors.forename: F D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: A
authors.initials: A
authors.lastname: Farb
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005466:Fluorocarbons / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D006895:Hydroxyethyl Starch Derivatives; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy*; D009504:Neutrophils / Q000502:physiology; D011817:Rabbits
chemical_list: D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination