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J Thorac Cardiovasc Surg 2004;127:1735-1742
© 2004 The American Association for Thoracic Surgery

Cardiopulmonary support and physiology

In vivo inhibition of neutrophil activity by a FAS (CD95) stimulating module: Arterial in-line application in a porcine cardiac surgery model

^a Department of Thoracic and Cardiovascular Surgery Johann Wolfgang Goethe University, Frankfurt am Main, Germany,
^b Central Animal Care and Research Facility, Johann Wolfgang Goethe University, Frankfurt am Main, Germany
^c Department of Trauma, Hand, and Reconstructive Surgery, Hamburg University School of Medicine, Hamburg, Germany

Received for publication April 24, 2003; revisions received September 8, 2003; accepted for publication September 10, 2003.

^* Address for reprints: Martin Scholz, PhD, Department of Thoracic and Cardiovascular Surgery, J.W. Goethe University, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany
m.scholz{at}em.uni-frankfurt.de

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 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.