In vivo inhibition of neutrophil activity by a FAS (CD95) stimulating module: arterial in-line application in a porcine cardiac surgery model.
OBJECTIVE
Cardiac surgery with cardiopulmonary bypass is associated with aberrant neutrophil activation and potentially severe pathogenic sequelae. This experimental study was done to evaluate a leukocyte inhibition module that rapidly inactivates neutrophils through CD95 stimulation.


METHODS
German landrace pigs (4 groups, each n = 5) underwent cardiac surgery without cardiopulmonary bypass (group I), with cardiopulmonary bypass (group II), with cardiopulmonary bypass plus a leukocyte filter (group III), and with cardiopulmonary bypass plus a leukocyte inhibition module (group IV). The leukocyte filter or leukocyte inhibition module was introduced into the arterial line of the heart-lung machine.


RESULTS
Leukocyte counts were decreased by up to 43% in group IV compared with values in group II (P =.023). In group IV, but not in groups I to III, no delay in spontaneous neutrophil apoptosis was observed after annexin V-propidium iodide staining. Late apoptotic (11.7%) or necrotic neutrophils (9.3%) were detected in 2 animals (group IV). Tumor necrosis factor alpha serum levels increased over time in groups I to III (>2-fold) but remained at baseline levels in group IV (P <.05). Interleukin 8-mediated chemotactic neutrophil transmigration activity increased over time in groups I to III but was totally abrogated in group IV at any time point. The perioperative increase of creatine kinase and creatine kinase MB levels was lower in groups III (1.5-fold and 1.3-fold, respectively) and IV (1.2-fold and 1.5-fold, respectively) compared with values in group II (both 1.9-fold).


CONCLUSIONS
The leukocyte inhibition module downregulated cardiopulmonary bypass-related neutrophil activity and thus might be beneficial in cardiac surgery and other clinical settings with unappreciated neutrophil activation.
Scholz
Martin
M
Department of Thoracic and Cardiovascular Surgery, Johann Wolfgang Goethe University, Frankfurt am Main, Germany. m.scholz@em.uni-frankfurt.de
Simon
Andreas
A
Berg
Markus
M
Schuller
Alina Maria
AM
Hacibayramoglu
Meltem
M
Margraf
Stefan
S
Theisen
Alf
A
Windolf
Joachim
J
Wimmer-Greinecker
Gerhard
G
Moritz
Anton
A
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006348:Cardiac Surgical Procedures / Q000379:methods*; D002315:Cardiopulmonary Bypass / Q000379:methods; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005374:Filtration / Q000295:instrumentation*; D007958:Leukocyte Count; D008297:Male; D015999:Multivariate Analysis; D018375:Neutrophil Activation / Q000187:drug effects*; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D013552:Swine; D019014:fas Receptor / Q000494:pharmacology*
D019014:fas Receptor