Differential effects of aprotinin and tranexamic acid on endotoxin desensitization of blood cells induced by circulation through an isolated extracorporeal circuit.
OBJECTIVE
To compare the effects of aprotinin and tranexamic acid on blood cytokine secretion induced by the circulation of blood through an isolated extracorporeal circuit.


METHODS
Prospective, placebo-controlled study.


METHODS
University hospital.


METHODS
Healthy volunteers (n = 18).


METHODS
Blood (400 mL) first was drawn from volunteers, then circulated through an isolated extracorporeal circuit. Three groups were compared depending on the addition or not of an antifibrinolytic agent in the circuit (control group [n = 8], tranexamic group [n = 5], aprotinin group [n = 5]). Samples for measurement were taken before and at different time points after the start of circulation through the extracorporeal circuit. Cytokine (tumor necrosis factor-alpha, interleukin [IL]-6, IL-8, and IL-10) concentrations in the plasma and in the supernatant of lipopolysaccharide-stimulated whole blood cell cultures were analyzed.


RESULTS
In the control and tranexamic acid groups, tumor necrosis factor-alpha, IL-6, and IL-10 secretion by whole blood cell cultures were rapidly decreased, whereas IL-8 secretion was unaffected. In the aprotinin group, IL-8 secretion was also decreased (p < 0.05).


CONCLUSIONS
These results show that aprotinin, but not tranexamic acid, modulates the inflammatory response by reducing the IL-8 secretion of blood cells activated by contact with foreign surfaces.
Asehnoune
Karim
K
Département Anesthésie-Réanimation, Hôpital Bichat-Claude Bernard, Assistance Publique-Hôpitaux de Paris, Paris, France.
Dehoux
Monique
M
Leçon-Malas
Véronique
V
Toueg
Marie-Laure
ML
Gonieaux
Marie-Hélène
MH
Omnes
Laurence
L
Desmonts
Jean-Marie
JM
Durand
Geneviève
G
Philip
Ivan
I
D000933:Antifibrinolytic Agents / Q000627:therapeutic use*; D007611:Aprotinin / Q000627:therapeutic use*; D001773:Blood Cells / Q000187:drug effects*; D003888:Desensitization, Immunologic; D004731:Endotoxins / Q000378:metabolism*; D005112:Extracorporeal Circulation; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D012016:Reference Values; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D013997:Time Factors; D014148:Tranexamic Acid / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000933:Antifibrinolytic Agents; D004731:Endotoxins; D015850:Interleukin-6; D016209:Interleukin-8; D015842:Serine Proteinase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D014148:Tranexamic Acid; D007611:Aprotinin