Significance of oxidants and inflammatory mediators in blood of patients undergoing cardiac surgery

BLOOD CONTACT WITH artificial surfaces within the extracorporeal circulation (ECC) triggers a chain of events that may induce a temporal change in the patient's own immune system.(1) The complex role played by the immune system in the ECC-mediated pathophysiology is not yet fully understood, although several interlinked mechanisms Could play a role. ECC-mediated pathophysiology may be triggered by a wide range of factors including the exposure of blood to non-physiologic surfaces and mechanical shear stresses, surgical trauma, anesthesia, changes in body temperature, increased intestinal permeation by endotoxins, and ischemia-reperfusion injury.(2) The combined action of these factors results in a complex immunologic reaction (Figs I and 2) propagated by blood leukocytes culminating with the release of reactive oxygen species (ROS) and arachidonic acid metabolites, endothelins, platelet-activating factors, proinflammatory cytokines, and endothelial and leukocyte adhesion molecules into circulation.(3,4) The clinical manifestation of this reaction is believed to include prolonged in-hospital stay and postoperative complications such as wound infections, respiratory failure, and myocardial damage causing cardiac contractile dysfunction and even heart failure, renal impairment, coagulopathy, neurologic dysfunction, altered liver function, and even increased mortality.(5) Emerging data 6,7 increasingly support the idea that oxidative stress may be a possible cause of ECC-induced inflammation because of an early activation of polymorphonuclear cells (PMNs) that leads to enhanced release of bursts of reactive oxygen species commonly termed as respiratory burst accompanied by progressive increases in plasma PMN elastase, interleukin (IL)-6, IL-8, and C-reactive protein (CRP) levels for up to 48 hours after the procedure, a time when the oxidative stress still continues to rise. In these latter stages of oxidative stress increase, the idea that the accumulation of newly synthesized inflammatory factors may be in part the key contributors/triggers for the release of more damaging oxidant species cannot be ruled out. However, the origin of the early phase of oxidative stress is still largely unclear, although evidence suggests that vascular atherosclerotic lesions may in part be a significant source.(8,9) The authors hypothesize that there is a direct effect of free radicals on the ECC-induced inflammatory reaction, although the understanding of the underlying mechanisms and the complexity of the reaction kinetics has remained elusive. This review discusses in detail the literature that supports the direct relationship between ECC-mediated oxidative stress and changes in systemic inflammatory reaction and outcomes of patients undergoing cardiac surgery as supported by evidence from experimental and clinical studies.