title: Effects of simulated extracorporeal circulation on human leukocyte elastase release, superoxide generation, and procoagulant activity.
abstract: Activated leukocytes are thought to contribute to respiratory dysfunction, alterations in microvascular permeability, disseminated intravascular coagulation, and thrombosis, all of which can complicate extracorporeal circulation. The purpose of this work was to determine the effects of extracorporeal circulation on leukocyte functions likely to mediate organ damage. White blood cell counts in the bubble circuits (n = 5) fell to 51% +/- 7% (mean +/- standard error of the mean; p less than 0.05) of initial levels within 2 hours of recirculation. In contrast, counts from both the spiral coil (n = 5) and hollow-fiber (n = 5) groups remained at 91% +/- 12% and 100%, respectively. Plasma levels of human neutrophil elastase rose from 0.28 +/- 0.06 micrograms/ml to 3.14 +/- 0.36 micrograms/ml (p less than 0.05) and 0.20 +/- 0.02 micrograms/ml to 1.61 +/- 0.35 micrograms/ml (p less than 0.05) in bubble and spiral coil circuits, respectively, but from only 0.20 +/- 0.03 micrograms/ml to 0.96 +/- 0.42 micrograms/ml in the hollow-fiber circuit despite 2 hours of recirculation. Consistently, in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine, a chemotactic peptide, cells from spiral coil and bubble circuits released and generated significantly less elastase and superoxide anion, respectively. In contrast, neutrophils from the hollow-fiber circuits demonstrated enhancement of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced elastase release and superoxide generation. Finally, mixed leukocytes from all circuits expressed procoagulant activity reaching statistical significance in bubble circuits. In conclusion, extracorporeal circulation has pronounced effects on neutrophil elastase release, superoxide anion generation, and leukocyte procoagulant activity. Spiral coil and bubble oxygenators cause granule release and, subsequently, reduced sensitivity to soluble agonists. In contrast, hollow-fiber oxygenators "prime" cells, actually enhancing reactivity. Recirculation through all circuits induces leukocyte procoagulant activity that is likely to contribute to surface-induced thromboses and excessive bleeding.
authors.affiliation: Temple University School of Medicine, Department of Surgery, Philadelphia, Pa 19140.
authors.forename: R F
authors.initials: RF
authors.lastname: Stahl
authors.forename: C A
authors.initials: CA
authors.lastname: Fisher
authors.forename: U
authors.initials: U
authors.lastname: Kucich
authors.forename: G
authors.initials: G
authors.lastname: Weinbaum
authors.forename: D S
authors.initials: DS
authors.lastname: Warsaw
authors.forename: N
authors.initials: N
authors.lastname: Stenach
authors.forename: C
authors.initials: C
authors.lastname: O'Connor
authors.forename: V P
authors.initials: VP
authors.lastname: Addonizio
mesh_terms: D001777:Blood Coagulation; D015199:Extracorporeal Membrane Oxygenation / Q000295:instrumentation; D006801:Humans; D007958:Leukocyte Count; D019272:Leukocyte Elastase; D007962:Leukocytes / Q000378:metabolism* / Q000502:physiology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase