Neutrophil activation in a roller pump model of cardiopulmonary bypass: Influence of biomaterial, platelets and complement
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Background: In cardiac surgery with cardiopulmonary bypass a complex systemic inflammatory response can arise postoperatively, causing serious complications such as the development of multi-organ dysfunction. Neutrophil granulocytes, representing 40-60% of the white blood cells, play a central role in the pathogenesis of the inflammatory reaction. Multiple factors can activate neutrophils: Contact between blood and the foreign surfaces of the heart-lung machine or activated/damaged endothelium, interaction with platelets and other blood cells, as well as components of the complement system and other plasma protein systems. Altered flow dynamics can also influence neutrophil activation. Certain neutrophil functions may be down-regulated postoperatively, which may be a risk factor for postoperative infections. Methods: We investigated the significance of biomaterial contact, platelets and complement in the activation of neutrophils. An in vitro cardiopulmonary bypass roller pump model was used, so that the influence of single factors could be studied. Neutrophil activation was evaluated by measuring neutrophil adhesion to the biomaterial, cultured human endothelial cells and gelatin, expression of surface receptors and degranulation. Since neutrophils are fragmented by the roller pump, we also investigated whether fragmented neutrophils could activate the complement system and whether platelets had any influence on neutrophil-mediated activation of complement. Results: In our model, the influence of biomaterial itself and the mechanical trauma by the roller pump on neutrophil activation was limited. Platelets and the complement system were of greater significance. Inhibiting neutrophil-platelet cross-talk by antibody-mediated blocking of relevant receptors, CD62P, CD42b or JAM-C, did not prevent neutrophil activation. Blocking of GPIIb/IIIa (CD41/CD61) with the drug abciximab showed some beneficial effects in the lower clinical dose range, as reduction of neutrophil degranulation and mixed aggregation of platelets and neutrophils. Neutrophil granulocytes were also found to partly lose their ability to adhere to endothelial cells following recirculation in the cardiopulmonary bypass model, whereas they increased their capacity for activation and their adhesiveness to the extracellular matrix. These results confirm that neutrophil granulocytes exposed to the extracorporeal circuit may contribute to postoperative organ damage. We also found that even though some neutrophils become fragmented by the roller pump, this has no clinically relevant impact on the complement system.
UtgiverNorges teknisk-naturvitenskapelige universitet, Det medisinske fakultet, Institutt for laboratoriemedisin, barne- og kvinnesykdommer
SerieDoktoravhandlinger ved NTNU, 1503-8181; 2008:104
Dissertations at the Faculty of Medicine, 0805-7680; 349