Enhanced Responsiveness of Circulatory Neutrophils After Cardiopulmonary Bypass: Increased Aggregability and Superoxide Producing Capacity

Abstract

Cardiac surgery with cardiopulmonary bypass (CPB) induces a whole body inflammatory response that sometimes leads to postoperative organ dysfunction, and neutrophil activation plays an important role in this reaction. Neutrophil priming has been described as a change in neutrophil status such that neutrophils show enhanced responsiveness to a second activating stimulus. We hypothesized that neutrophil priming occurs by cardiac surgery with CPB and is temporally related to the neutrophilia after surgery. To evaluate primed circulatory neutrophil status, we measured aggregation activity stimulated by N-formyl-methyl-leucyl-phenyl-alanine (FMLP) and free radical producing activity by tumor necrosing factor (TNF) alpha in peripheral blood samples. Eleven adult patients undergoing elective cardiac surgery with CPB were studied. Blood samples were taken before surgery, at the end of bypass, 12 h after surgery, and 7 days after surgery. Aggregation activity and superoxide generation were significantly elevated 12 h after surgery when compared to presurgery values, indicating that cardiac surgery is associated with circulatory neutrophil priming. The number of neutrophils markedly increased at the end of cardiopulmonary bypass and reached a peak 12 h after surgery. The circulatory neutrophils of cardiac surgical patients become primed after surgery, coincident with the peak neutrophil count. These results suggest that circulatory neutrophils after cardiac surgery with CPB have enhanced responsiveness and are predisposed to systemic inflammation.

The pathogenesis of transfusion‐related acute lung injury (TRALI)

“…It should be kept in mind that linking TRALI to any specific clinical event needs valid denominator data. However, some of these observations are in accordance with in vivo evidence from studies demonstrating that surgical procedures and active infections induce neutrophil priming in patients (Bass et al, 1986;Krause et al, 1988;Kawahito et al, 2000). A variety of neutrophil priming agents that are released either by dying/necrotic cells or by stimulated endothelial cells, monocytes and lymphocytes have been described, including platelet activating factor (PAF) (Vercellotti et al, 1988), tumour necrosis factor-a (TNF-a) (Berkow et al, 1987), interleukin 8 (IL-8) (Daniels et al, 1992), granulocyte/macrophage-colony stimulating factor (Fleischmann et al, 1986), and interferon-c (Tennenberg et al, 1993).…”

Simvastatin attenuates leucocyte-endothelial interactions after coronary revascularisation with cardiopulmonary bypass

“…Moreover, cardiopulmonary bypass itself causes local injury secondary to an acute inflammatory response that involves tissue infiltration by activated neutrophils and platelets. [5][6][7][8][9] The mechanism of endothelial dysfunction and reduced NO bioavailability in ischaemia/ reperfusion injury is still being debated. Data from studies in animals suggest that there might either be reduced substrate for NO synthesis 10 or increased NO inactivation by neutrophil released superoxide.…”

“…First, cardiopulmonary bypass itself is characterised by an inflammatory response in which the activated polymorphonuclear leucocytes (neutrophils) play an important role, [5][6][7] mediating coronary and pulmonary endothelial injury by both capillary plugging of the myocardial microvasculature and release of reactive oxygen species, inflammatory cytokines, and proteolytic enzymes. 8 9 Many of these substances in turn also mediate vascular endothelial dysfunction, characterised by loss of the ability of the endothelium to synthesise and release nitric oxide (NO).…”

Association of Preoperative Platelet-to-Lymphocyte Ratio with Atrial Fibrillation after Coronary Artery Bypass Graft Surgery

“…The presence of this postoperative AF has been known to be due to the contribution of systemic inflammation mediated by various proinflammatory cytokines, such as IL-6, IL-8, and TNF-α [11] . In addition to their role in the inflammatory cascade, these proinflammatory cytokines along with leukocyte count and neutrophil-to-lymphocyte ratio have been reported to be higher in patients with AF after CABG surgery than those without AF [12][13][14] . However, no data exists regarding the association between PLR (a marker of inflammation) and AF after CABG surgery.…”