Prevention of neutrophil-mediated injury to endothelial cells by perfluorochemical.
Myocardial salvage after reperfusion may be limited by neutrophil-mediated microvascular damage. The effect of the perfluorochemical, Fluosol-DA, and its various components on neutrophil adherence, cytotoxicity, and proteolytic enzyme release was examined on sheep large and small vessel endothelial cells in vitro. Cells were studied under normoxic (N) and anoxic conditions (A). Various concentrations of Fluosol (10%, 25%, and 50%) significantly reduced neutrophil adherence under both experimental conditions [mean 22 +/- 3.25% versus 7 +/- 0.8% (N) and 20 +/- 3.2% versus 7.5 +/- 0.9% (A); P less than 0.01]. The perfluorocarbons, perfluorodecalin (PFD), and perfluoro-tripropylamine (PFTP) in a 50 volume/percent concentration exhibited profound effects on adherence, particularly on cells subjected to anoxia (51% and 69% reduction in adherence, respectively; P less than 0.01). No effect on adherence was observed with other components, including the detergent, pluronic F68. A 25% reduction (P less than 0.02) in endothelial cytotoxicity was noted when neutrophils were preincubated with Fluosol. However, pretreatment of endothelial cells with Fluosol did not inhibit neutrophil adherence. Neutrophils stimulated with cytochalasin B and FMLP showed a significant reduction in lysozyme release after incubation with Fluosol (28 +/- 5% versus 17 +/- 4%; P less than 0.01). This study demonstrates that Fluosol significantly attenuates neutrophil adherence, cytotoxicity, and enzyme release in an in vitro model of microvascular injury. It also suggests that prevention of neutrophil-mediated microvascular damage may be an important mechanism whereby Fluosol enhances myocardial salvage after ischemia and reperfusion.
Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232-2170.
D G
DG
Babbitt
M B
MB
Forman
R
R
Jones
A K
AK
Bajaj
R L
RL
Hoover
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004338:Drug Combinations / Q000494:pharmacology / Q000633:toxicity; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D005466:Fluorocarbons / Q000494:pharmacology* / Q000633:toxicity; D006895:Hydroxyethyl Starch Derivatives; D000860:Hypoxia / Q000473:pathology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010447:Peptide Hydrolases / Q000378:metabolism; D011060:Poloxalene / Q000494:pharmacology / Q000633:toxicity; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012756:Sheep
D004338:Drug Combinations; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D011838:Radiation-Sensitizing Agents; D009240:N-Formylmethionine Leucyl-Phenylalanine; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; D011060:Poloxalene; D010447:Peptide Hydrolases