Introduction Cardiac surgery with cardiopulmonary bypass (CPB) is a recognized trigger of systemic inflammatory response, usually related to postoperative acute lung injury (ALI). As an attempt to dampen inflammatory response, steroids have been perioperatively administered to patients. Macrophage migration inhibitory factor (MIF), a regulator of the endotoxin receptor, is implicated in the pathogenesis of ALI. We have previously detected peak circulating levels of MIF, 6 hours post CPB. Experimental data have shown that steroids may induce MIF secretion by mononuclear cells. This study aims to correlate levels of MIF assayed 6 hours post CPB to the intensity of postoperative pulmonary dysfunction, analysing the impact of perioperative steroid administration. MethodsWe included patients submitted to cardiac surgery with CPB, electively started in the morning, performed by the same team under a standard technique except for the addition of methylprednisolone (15 mg/kg) to the CPB priming solution for patients from group MP (n = 37), but not for the remaining patients -group NS (n = 37). MIF circulating levels were assayed at the anesthesia induction, 3, 6, and 24 hours after CPB. A standard weaning protocol with fast track strategy was adopted, and indicators of organ dysfunction and therapeutic intervention were registered during the first 72 hours postoperative.Results Levels of MIF assayed 6 hours post CPB correlated directly to the postoperative duration of mechanical ventilation (P = 0.014, rho = 0.282) and inversely to PaO 2 /FiO 2 ratio (P = 0.0021, rho = -0.265). No difference in MIF levels was noted between the groups. The duration of mechanical ventilation was higher (P = 0.005) in the group MP (7.92 ± 6.0 hours), compared with the group NS (4.92 ± 3.6 hours). ConclusionCirculating levels of MIF assayed 6 hours post CPB are correlated to postoperative pulmonary performance. Immunosuppressive doses of methylprednisolone did not affect circulating levels of MIF and may be related to prolonged mechanical ventilation. P2Immediate and short-term safety of catheter-based autologous bone marrow-derived mononuclear cell transplantation into myocardium of patients with severe ischemic heart failure Background Bone marrow-derived mononuclear cell (BM-MNC) transplantation into the myocardium has been proposed as a new therapy for ischemic heart failure (HF). Successful cellular therapy for HF using myoblast transplantation has been reported previously but malignant arrhythmias (MA) were an issue. We investigated the safety of BM-MNC transplantation into the myocardium for MA.Methods A prospective study to evaluate the safety of autologous BM-MNC transplantation in patients with severe ischemic HF not amenable to myocardial revascularization was conducted. Bone marrow was harvested from the iliac crest and BM-MNCs were selected by Ficoll gradient. Hibernating myocardium areas were targeted using electromechanical mapping in catheter-based subendocardial injections (MyoStar, Cordis, Miami Lakes, FL, USA). All patien...
CARDIOLOGY P1 Impact of peroperative administration of steroid over inflammatory response and pulmonary dysfunction following cardiac surgery
Introduction Neutrophils have been involved in sepsis-induced organ damage. Neutrophils could be directly activated by TLR binding ligands including LPS. IRAK-1 is one of many intracellular proteins that are activated upon stimulation of TL receptors. This triggers a series of events that results in the migration of NF-κB into the nucleus and the activation NF-κB-dependent genes. Objectives To identify a single nucleotide polymorphism at position 532 (coding SNP) in volunteers and patients with sepsis. To determine whether IRAK-1 SNP532 results in a decrease in neutrophil NF-κB activation in volunteers and patients with sepsis. To evaluate neutrophil gene expression patterns in IRAK-1 SNP532 and wildtype patients with sepsis. Methods Thirty severe sepsis patients and 34 healthy volunteers were enrolled in this study. Peripheral blood was obtained and neutrophils were isolated by plasma-percoll gradients after dextran sedimentation of erythrocytes. Neutrophils from volunteers were resuspended in RPMI and cultured with or without 100 ng/ml LPS for 60 min. The electrophoretic mobility shift assay technique was used to measure the NF-κB activation. Real-time PCR allelic discrimination assays were developed by the assay-by-design service offered by Applied Biosystems (Foster City, CA, USA). Probe and primer combinations were designed at the single nucleotide polymorphism 532. PCR reactions were performed according to the manufacturer's manual using the Applied Biosystems 7500 Real-Time PCR system. Microarray analysis was used to evaluate the neutrophil gene expression in unstimulated neutrophils and after LPS stimulus. Results The median AUC for NF-κB activation was higher in wildtype genotyped neutrophils as compared with IRAK-1 SNP532 genotyped neutrophils (85.2 vs 100.5, P = 0.05) (Fig. 1). In terms of kinetics pattern, we found some differences on nuclear levels of NF-κB in neutrophils from volunteers cultured with LPS. At 30 min after LPS, the culture nuclear translocation of NK-κB was significantly greater in wildtype genotyped neutrophils than in IRAK-1 SNP532 genotyped neutrophils. Even after 60 min, the NF-κB translocation remained high in wildtype genotyped neutrophils, while in IRAK-1 SNP532 genotyped neutrophils the NF-κB translocation was similar to baseline (Fig. 2). In unstimulated neutrophils from septic patients, the NF-κB translocation was significantly lower in IRAK-1 SNP532 genotyped neutrophils than in wildtype genotyped neutrophils (1.20 vs 2.10, P = 0.05) (Fig. 3). Finally, the expression of some inflammatory related genes (IL-8, IL1β, MIP-2, COX-2, and SOD2) was decreased in IRAK-1 SNP532 genotyped neutrophils. Conclusion IRAK-1 SNP532 genotyped neutrophils from volunteers (after LPS ex vivo challenge) and from septic patients are associated with lower NF-κB activation and lower expression of some IRAK1-related genes. These results demonstrate that IRAK1 Introduction Neutrophils play a major role in sepsis-induced organ dysfunction, especially in the lung. HMGB1 has emerged as a late cytokine...
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