Prediction of clinical outcome after cardiac surgery: the role of cytokines, endotoxin, and anti-endotoxin core antibodies.
ABSTRACT Coronary artery bypass grafting (CABG) using cardiopulmonary bypass (CPB) can lead to a systemic inflammatory response syndrome with organ failure and increased morbidity and mortality. The mechanisms of these findings are still under discussion. We investigated whether anti-endotoxin core antibodies, endotoxin, and proinflammatory cytokines influence the clinical course after cardiac surgery. Seventy-eight patients undergoing CABG using CPB were investigated. Anti-endotoxin core antibodies, endotoxin, interleukin (IL)-6, IL-8, IL-1beta, and TNF-alpha were measured 24 h preoperatively and up to 72 h postoperatively. Patients with a postoperative mechanical ventilation time below 24 h (n = 65; Group A) were compared to patients with prolonged respirator therapy (>24 h; n = 13; Group B). Preoperative antibody levels were significantly lower in Group B (P < 0.001). In this group, antibody levels remained decreased during the observation period (P < 0.001). Endotoxin significantly increased 30' postoperatively in both groups (P < 0.002). The increase in Group B was 3-fold higher (P< 0.001). IL-8 increased postoperatively in both groups, peaking 3 h after surgery (P < 0.001). In Group B, the IL-8 release was significantly higher than in Group A (P < 0.001). IL-6 significantly increased in both groups, reaching its maximum 24 h postoperatively (P < 0.001). No differences between groups were observed. No significant changes of IL-1beta and TNF-alpha were observed. We conclude that anti-endotoxin core antibodies may be predictive of adverse outcome after cardiac surgery. The imbalance between antibodies and endotoxin results in an exaggerated increase in endotoxin and IL-8 with an impact on clinical outcome.
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ABSTRACT: Cardiac surgery induces a systemic inflammatory activation, which in severe cases is associated with peripheral vasodilation and hypotension. Cardiotomy suction blood contains high levels of inflammatory mediators, but the effect of cardiotomy suction blood on the vasculture is unknown. We investigated the effect of cardiotomy suction blood on systemic vascular resistance in vivo and whether cell-saver processing of suction blood affects the vascular response. Twenty-five patients undergoing coronary surgery (mean age, 68 +/- 2 years; 80% men) were included in a prospective randomized study. The patients were randomized to retransfusion of cell-saver processed (n = 13) or cell-saver unprocessed (n = 12) suction blood during full cardiopulmonary bypass. Mean arterial blood pressure was continuously registered during retransfusion, and systemic vascular resistance was calculated. Plasma concentrations of tumor necrosis factor alpha, interleukin 6, and complement factor C3a were measured in suction blood. Retransfusion of cardiotomy suction blood induced a transient reduction in systemic vascular resistance in all patients. The peak reduction was significantly less pronounced in the group receiving cell-saver processed blood (-12% +/- 2% vs -28% +/- 3%, P = .001). There was a significant correlation between tumor necrosis factor alpha concentration in retransfused cardiotomy suction blood and peak reduction of systemic vascular resistance (r = 0.60, P = .002). The results suggest cardiotomy suction blood is vasoactive and might influence vascular resistance and blood pressure during cardiac surgery. The observed vasodilation is proportional to the inflammatory activation of suction blood and can be reduced by processing suction blood with a cell-saving device before retransfusion.The Journal of thoracic and cardiovascular surgery 07/2006; 131(6):1352-7. · 3.41 Impact Factor
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ABSTRACT: A systemic inflammatory response is not uncommonly observed after coronary revascularization. Tumor necrosis factor alpha is one of a number of modulators of this response. A functional polymorphism within the TNFalpha gene at position G-308A has been associated with increased TNFalpha levels. The relationship between predicted TNFalpha genotype and circulating TNFalpha levels in patients undergoing coronary revascularization surgery has yet to be defined. We examined the relationship between TNFalpha G-308A polymorphism, TNFalpha postoperative levels, and clinical outcome after coronary revascularization surgery. We obtained DNA from 96 consecutive patients who underwent elective coronary revascularization. Patients were genotyped for TNFalpha G-308A polymorphism using sequence specific primer-polymerase chain reaction (SSP-PCR). Tumor necrosis factor alpha levels were measured on serum samples taken 3 hours postoperatively using enzyme-linked immunosorbent assay (ELISA). The prevalence of AA, AG, and GG TNFalpha-308 genotype was 12%, 40%, and 48%, respectively. Patients homozygous for A had higher circulating levels of TNFalpha (p = 0.009). Higher levels of TNFalpha were significantly associated with prolonged intensive care unit stay (p = 0.008), increase usage of an inotropic agent (p = 0.024), increased mortality risk (p = 0.018), and diabetes (p = 0.019). These remained statistically significant after risk stratification. Patients of the AA-308 TNFalpha genotype showed significantly higher TNFalpha plasma levels. Higher plasma levels of TNFalpha were associated with less favorable outcome after coronary revascularization surgery. It may prove useful to utilize TNFalpha serum levels as a marker for identifying high-risk patients in the future.The Annals of thoracic surgery 02/2006; 81(1):132-7. · 3.74 Impact Factor
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ABSTRACT: Laboratory and clinical data have implicated endotoxin as an important factor in the inflammatory response to cardiopulmonary bypass. Alkaline phosphatase prevents endotoxin-induced systemic inflammation in animals and humans. We assessed the effects of the administration of bovine intestinal alkaline phosphatase on surgical complications in patients undergoing coronary artery bypass grafting. In a double blind, randomized, placebo-controlled study, a total of 63 patients undergoing coronary artery bypass grafting were enrolled. Bovine intestinal alkaline phosphatase or placebo was administered as an intravenous bolus followed by continuous infusion for 36 hours. The primary endpoint was reduction of post-surgical inflammation. No significant safety concerns were identified. The overall inflammatory response to coronary artery bypass grafting with cardiopulmonary bypass was low in both placebo and bovine intestinal alkaline phosphatase patient group. Five patients in the placebo group displayed a significant TNFalpha response followed by an increase in plasma levels of IL-6 and IL-8. Such a TNFalpha response was not observed in the bovine intestinal alkaline phosphatase group, suggesting anti-inflammatory activity of bovine intestinal alkaline phosphatase. Other variables related to systemic inflammation showed no statistically significant differences. Bovine intestinal alkaline phosphatase can be administered safely in an attempt to reduce the inflammatory response in coronary artery bypass grafting patients with a low to intermediate EuroSCORE. The anti-inflammatory effects might be more pronounced in patients developing more fulminant postoperative inflammatory responses. This will be investigated in a further trial with inclusion of patients undergoing complicated cardiac surgery, demanding extended cardiopulmonary bypass and aortic cross clamp time. In this review article some recent patents related to the field are also discussed.Recent Patents on Inflammation & Allergy Drug Discovery 12/2009; 3(3):214-20.