Multimodal monitoring of neutrophil activity during cardiac surgery

Darko Jovanovski ¹ Lisa Wohlgemuth ² Pascal Max Lucien Lessing ² Dominik Hüsken ² Alexander Sebastian Koller ² Bertram Thomaß ² Paul Müller ² Marco Mannes ² Sandra Nungeß ³ Marta Jovanovska ¹ Bernd Mühling ¹ Andreas Liebold ¹ Markus Huber-Lang ¹ David Alexander Christian Messerer ^2,4*

• ¹ Department of Cardiothoracic and Vascular Surgery, University Hospital Ulm, Ulm, Germany
• ² Institute of Clinical and Experimental Trauma Immunology, Ulm, Germany
• ³ Institute of Transfusion Medicine, Ulm, Germany
• ⁴ Ulm University Medical Center, Ulm, Germany

Cardiac surgery and associated ischemia-reperfusion injury trigger an inflammatory response, which in turn can contribute to organ damage, prolonged hospitalization, and mortality. Therefore, the present study performed a comprehensive monitoring of the neutrophil-related inflammation in patients who underwent aortic valve surgery, including extracorporeal circulation. Neutrophil-related inflammation as well as alterations in cellular physiology, phenotype, and function were mainly analyzed by flow cytometry, ELISA, and microscopy. Neutrophil activation occurred intraoperatively and preceded upregulation of conventional inflammatory markers such as c-reactive protein and interleukin-6. Perioperatively, neutrophils maintained a stable response to platelet-activating factor (PAF) with regard to CD11b and CD66b expression, but showed a decreased response in CD10. Postoperatively, neutrophils exhibited marked altered PAF-induced depolarization, while reactive oxygen species generation and phagocytic activity remained largely stable. Surprisingly, platelet-neutrophil complex formation was severely impaired intraoperatively but returned to normal levels postoperatively. Further studies need to elucidate the implications of these intraoperative and postoperative changes in neutrophil and platelet activity with respect to a potential immune dysfunction that temporarily increases susceptibility to infectious or hemostatic complications.