体外循环炎症反应中粘附分子变化及干预性治疗的研究

目的探讨体外循环(CPB)围术期中药川芎嗪干预性治疗的作用机制及临床意义.方法选取诊断明确的先天性心脏病病人32例,随机分成川芎嗪组20例,对照组12例.前者在体外循环预充液中加入盐酸川芎嗪5 mg/kg,后者不用.分别于麻醉诱导后,转机15 min,停机2、6、12、24 h共6个时点,抽取动脉血,采用双抗体夹心法酶联免疫吸附试验测定血浆中可溶性细胞间粘附分子(sICAM-1)、可溶性P-选择素(sP-Selectin)的表达值.结果麻醉诱导后(基值)川芎嗪组和对照组sICAM-1、sP-Selectin无明显差异(P＞0.05);转机后15 min、停机2、6、12 h两组的sICAM-1、sP-Selectin表达值均明显升高,其中停机6、12 h最为明显,与基值比较 ,差异有显著性(P＜0.05);但川芎嗪组较对照组为低(P＜0.05).结论川芎嗪能减弱CPB致炎症反应中sICAM-1、sP-Selectin表达,减轻CPB所致炎症反应,从而减少CPB下心脏直视手术并发症的发生.     

Effect of normothermic versus hypothermic cardiopulmonary bypass on cytokine production and platelet function

BACKGROUND: Proinflammatory cytokines and platelets play a key role in the systemic inflammatory response associated with cardiopulmonary bypass (CPB). The aim of this study was to evaluate the effects of both hypothermic and normothermic CPB on platelet activation, cytokine production, as well as their possible correlations. METHODS: Twenty patients who underwent CABG were randomly assigned into two groups receiving hypothermic and normothermic CPB. Blood samples were obtained through a venous catheter at 6 time points. The following parameters were measured: in vitro platelet aggregation, in vivo platelet activation, complete and differential blood cell counts, plasma soluble P-selectin levels, plasma IL-6, IL-1beta and TNFalpha levels. RESULTS: The results demonstrated that platelet abnormalities could be observed to a greater extent during hypothermic rather than normothermic CPB. The occurrence of in vivo platelet activation was suggested by the presence of a significantly increased percentage of platelets expressing CD62P on their surface, as well as by a decreased in vitro platelet aggregation induced by different agonists. Complete and differential blood cell counts showed no substantial decrease in platelet number without differences between groups. The results obtained also showed the presence of a significant release of sP-selectin during CPB, as well as a more pronounced increase of plasma sP-selectin levels in patients undergoing hypothermic compared to normothermic CPB. A comparison of cytokine levels demonstrated a significant elevation of plasma IL-6 levels during either hypothermic or normothenmic CPB, paralleling the neutrophil rise, while no differences were observed for TNF-alpha levels. Conversely, plasma IL-1beta levels were significantly elevated during hypothermic, but not during normothermic CPB. CONCLUSIONS: Hypothermic CPB is responsible for a greater platelet activation and endothelial dysfunction than normothermic CPB, leading to more profound changes in the hemostatic and inflammatory systems, which, in turn, might be responsible for the higher incidence of postoperative complications reported during hypothermic CPB.     

Beta-chemokine secretion patterns in relation to clinical course and outcome in children after cardiopulmonary bypass: continuing the search to abrogate systemic inflammatory response

BACKGROUND: Surgery involving cardiopulmonary bypass (CPB) is frequently accompanied by a systemic inflammatory response partly triggered by neutrophils and monocyte-macrophages. Certain cytokines that are powerful leukocyte-chemotactic factors have recently been characterized and shown to be important in evoking inflammatory responses: monocyte chemoattractant protein-1 (MCP-1) has monocyte-macrophage chemotactic activity, and regulated-upon-activation normal T-cell expressed and secreted (RANTES) has a potent chemoattractant activity for mononuclear phagocytes. This prospective cohort study investigated possible roles of these chemokines in the inflammatory response to CPB and relationships between the changes in chemokine levels and the clinical course and outcome. METHODS: Systemic blood of 16 children undergoing CPB was collected after induction of anesthesia (base line); at 15 minutes after bypass onset; at CPB cessation; and at 1, 2, 4, 8, 12, and 24 hours afterward to measure MCP-1 and RANTES. RESULTS: The significant changes of plasma beta chemokine levels following CPB were associated with patient characteristics, operative variables, and postoperative course. Cardiopulmonary bypass of more than 2 hours, longer surgical times, inotropic support, and reoperation were associated with higher MCP-1 levels and lower RANTES levels. CONCLUSIONS: Our results suggest a relation between CPB-induced mediators and clinical effects, implying pathogenic roles for chemokines following CPB. These molecules should be considered as possible targets for therapeutic intervention.     

Soluble Adhesion Molecules and Myocardial Injury during Coronary Artery Bypass Grafting

Abstract Cardiopulmonary bypass is acknowledged to be one of the major causes of a complex systemic inflammatory response after cardiac surgery. Leukocyte-endothelial binding followed by neutrophil migration appears to play a central role. These interactions are mediated by adhesion molecules on the surface of activated cells. The present study compared the perioperative levels of soluble adhesion molecules after coronary artery bypass grafting (CABG) in patients with or without cardiopulmonary bypass (CPB). Altogether, 9 patients underwent off-pump revascularization and 11 did so with CPB. Plasma levels of soluble adhesion molecules sE-selectin and sP-selectin and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before anesthesia induction and 1, 4, and 20 hours after reperfusion to the myocardium. The baseline plasma levels of the adhesion molecules were similar in the two groups. Perioperative levels of sE-selectin remained the same and did not differ between groups. Plasma sP-selectin increased in both groups, the change being significantly greater in the CPB group than that in the off-pump group (p = 0.001). Plasma sICAM-1 decreased during an early stage after CABG with CPB, recovering at 4 hours after reperfusion; and a significant increase in ICAM-1 was observed 20 hours later. In the off-pump group, sICAM-1 levels did not change at 1 and 4 hours after reperfusion but increased 20 hours later. Postoperative creatine kinase–muscle bound (CK-MB) levels were significantly higher in the CPB group than in the off-pump group (p = 0.001). The change in sP-selectin levels also showed a correlation with CK-MB values (r = 0.676, p = 0.001). The results indicated that off-pump revascularization is associated with reduced endothelial activation and myocardial injury.     

Plasma-soluble E-selectin after cardiopulmonary bypass in children: is it a marker of the postoperative course?

OBJECTIVE: To investigate the relationship and possible role of soluble adhesion molecule E-selectin in the postoperative course in children undergoing cardiopulmonary bypass (CPB). DESIGN: Prospective cohort study. SETTING: Pediatric intensive care unit of a university hospital. PARTICIPANTS: Thirteen children who were candidates for cardiac surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serial blood samples of 13 CPB patients were collected from the arterial catheter or from the bypass circuits preoperatively; on initiation of CPB; on termination of CPB; and 1, 2, 4, 8, 12, 18, 24, and 48 hours postoperatively. Plasma was recovered immediately, aliquoted, and frozen at -70 degrees C until use. Circulating soluble selectin molecules were measured with a sandwich enzyme-linked immunosorbent assay technique. There were significant changes in plasma levels of soluble E-selectins in patients after CPB, and these levels were associated with patient characteristics, operative variables, and postoperative course. Soluble E-selectin correlated significantly with inotropic support and the use of anti-inflammatory drugs. There was a significant association between the development of postoperative sepsis and soluble E-selectin levels. No correlation was found between soluble E-selectins and duration of CPB, aortic cross-clamping, or hemodynamic variables, including heart rate and mean systemic arterial pressure. CONCLUSION: These results suggest a relationship between CPB-induced mediators and early and late clinical effects. Although the mechanism for the increase of soluble E-selectin remains to be elucidated, the upregulation of soluble E-selectin indicates neutrophil activation, and its inhibition may represent a target for reducing the inflammatory response associated with CPB.     

Interleukin-8 secretion following cardiopulmonary bypass in children as a marker of early postoperative morbidity

BACKGROUND: Interleukin (IL)-8, an 8 kDa peptide, is the first chemoattractant identified as being specific for neutrophils. Its possible association with early postoperative morbidity following cardiopulmonary bypass (CPB) in infants and children is unknown. This prospective cohort study sought possible roles of IL-8 in the inflammatory response to CPB and investigated if changes in IL-8 levels and clinical course and outcome were related. METHODS: IL-8 levels were measured in 16 children undergoing CPB. Systemic blood was collected after induction of anaesthesia (baseline), at 15 min after CPB onset and cessation, and at 1, 4, 8, 12 and 24 h thereafter. RESULTS: Correlation coefficients between IL-8 levels and CPB time ranged from 0.45 to 0.55, heart rate 0.41--0.44, surgical time 0.41--0.63 and pH --0.56 to --0.50 (P < 0.05 for all parameters). Univariate analyses showed that patients requiring inotropic support and those with tachycardia had significantly higher postoperative IL-8 levels (P < 0.05). Furthermore, IL-8 levels were significantly higher in patients with surgical times > 200 min and in patients with an aortic clamp in place for > 65 min. CONCLUSIONS: There was an association between IL-8 and early postoperative heart rate, and the need for inotropic support IL-8 correlated positively with surgical time, CPB time and heart rate and negatively with pH. IL-8 release may be related to some of the haemodynamic changes in the early postoperative course following CPB. The relationship between IL-8 and late markers of patient outcome in high-risk infants awaits further studies.     

Soluble Adhesion Molecules in Coronary Surgery and Cardiopulmonary Bypass with Pump Prime Aprotinin

Objective : The purpose of the present study was to establish whether pump prime aprotinin could influence soluble adhesion molecules in patients undergoing elective coronary artery bypass surgery. Design : Thirty patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg of aprotinin in the pump prime. Plasma levels of soluble adhesion molecules were analyzed perioperatively. Results : There were no significant changes in plasma sE-selectin after the operation in either group. Plasma sP-selectin increased significantly up to 20 h after reperfusion to the myocardium. Plasma sICAM-1 decreased in the early stage after cardiopulmonary bypass (CPB), then recovered at 4 h after reperfusion and a significant increase in sICAM-1 was observed 20 h later. There were no significant differences between the groups in postoperative changes in sP-selectin ( p = 0.21) and sICAM-1 ( p = 0.91). Conclusion : Pump prime aprotinin did not influence plasma levels of E-selectin, P-selectin and ICAM-1 in the present patients. The present results do not support the concept of an anti-inflammatory effect of pump prime aprotinin.     

Soluble adhesion molecules in coronary surgery and cardiopulmonary bypass with pump prime aprotinin

OBJECTIVE: The purpose of the present study was to establish whether pump prime aprotinin could influence soluble adhesion molecules in patients undergoing elective coronary artery bypass surgery. DESIGN: Thirty patients admitted for first-time elective coronary artery bypass surgery were randomized into control or aprotinin groups. Patients in the aprotinin group received 280 mg of aprotinin in the pump prime. Plasma levels of soluble adhesion molecules were analyzed perioperatively. RESULTS: There were no significant changes in plasma sE-selectin after the operation in either group. Plasma sP-selectin increased significantly up to 20 h after reperfusion to the myocardium. Plasma sICAM-1 decreased in the early stage after cardiopulmonary bypass (CPB), then recovered at 4 h after reperfusion and a significant increase in sICAM-1 was observed 20 h later. There were no significant differences between the groups in postoperative changes in sP-selectin (p = 0.21) and sICAM-1 (p = 0.91). CONCLUSION: Pump prime aprotinin did not influence plasma levels of E-selectin, P-selectin and ICAM-1 in the present patients. The present results do not support the concept of an anti-inflammatory effect of pump prime aprotinin.     

Preoperative administration of steroids: influence on adhesion molecules and cytokines after cardiopulmonary bypass

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with tissue damage mediated by adhesion molecules and cytokines. Prebypass steroid administration may modulate the inflammatory response, resulting in improved postoperative recovery. METHODS: Fifty patients undergoing elective coronary operations under normothermic CPB were randomized into two groups: group A (n = 24) received intravenous methylprednisolone (10 mg/kg) 4 hours preoperatively, and group B (n = 26) served as controls. Cytokines (tumor necrosis factor-alpha [TNF-alpha], interleukin-2R [IL-2R], IL-6, IL-8), soluble adhesion molecules (sE-selectin, sICAM-1), C-reactive protein, and leukocytes were measured before steroid application, then 24 and 48 hours, and 6 days postoperatively. Adhesion molecules were measured by enzyme-linked immunosorbent assay, cytokines by chemiluminescent immunoassay. Postoperatively, hemodynamic measurements, inotropic agent requirements, blood loss, duration of mechanical ventilation, and intensive care unit stay were compared. RESULTS: Aortic cross-clamp and CPB time was similar in both groups. Prednisolone administration reduced postoperative levels of IL-6 (611 versus 92.7 pg/mL; p = 0.003), TNF-alpha (24.4 versus 11.0 pg/L, p = 0.02), and E-selectin (327 versus 107 ng/mL, p = 0.02). Postoperative recovery did not differ between groups. CONCLUSIONS: Preoperative administration of methylprednisolone blunted the increase of IL-6, TNF-alpha, and E-selectin levels after CPB but had no measurable effect on postoperative recovery.     

Is hypothermia a benefit? Von Willebrand factor in pediatric cardiopulmonary bypass

AIM: The use of cardiopulmonary bypass (CPB) is associated with the risk of development of postpump syndrome. Thrombocyte activation leads to microembolism, endothelial damage and necrosis with release of various substances, such as the von Willebrand factor (vWf). High levels of vWf increase the risk of postoperative complications and mortality. Our objective was to find a correlation between CPB and plasma levels of vWf in pediatric patients operated on for congenital heart defects. METHODS: Twenty patients with congenital heart defects (ventricular septal defect, atrial septal defect/partial anomalous pulmonary vein drainage, Bland White Garland syndrome) were operated on with the use of CPB. The arterial blood was sampled after induction of anesthesia, 5 minutes after commencing CPB, 1 hour and 3 hours after surgery. The plasma levels of vWf were measured and compared to selected clinical findings. RESULTS: There was no early mortality. There were no significant differences in CPB and aortic cross clamp times when compared in patients with various defects. vWf plasma levels were significantly elevated in all patients 1 hour and 3 hours after surgery. We found no correlation between vWf levels and type of defect, CPB duration, aortic cross clamp as well as reperfusion time. However, we were able to demonstrate that the observed elevation of vWf levels was almost 4-fold higher in patients cooled down to lower temperatures (15 patients; mean rectal value 27.64+/-0.7 degrees C) than in 5 patients (mean rectal temperature 30.74+/-1.56 degrees C) where only slight elevation was found. There were no differences in the postoperative course of these patients. All patients were discharged from hospital 10+/-3 days after operation (mean value 9 days). CONCLUSIONS: vWf plasma levels are significantly elevated after pediatric hypothermic CPB. It seems that the augmentation of vWf values could be independently associated with rate of hypothermia.     

Inflammatory response after coronary revascularization: off-pump versus on-pump (heparin-coated circuits and poly2methoxyethylacrylate-coated circuits).

OBJECTIVE: Off-pump coronary artery bypass grafting (OPCAB) may reduce the inflammatory response associated with cardiopulmonary bypass (CPB) and contribute to minimizing postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits were developed to reduce such complications. We compared the postoperative inflammatory response with or without CPB. METHODS: Eighteen consecutive patients undergoing isolated coronary artery bypass grafting (CABG) were divided into three groups: OPCAB group (n=6), heparin-coated circuits group (n=6), PMEA-coated circuits group (n=6). The plasma concentrations of the following inflammatory markers were measured: cytokines [interleukin (IL-10)], polymorphonuclear elastase (PMNE), coagulofibrinolytic factor [thrombin-antithrombin III complex (TAT)], complement factor (C3a). RESULTS: At the end of CPB, IL-10 and TAT concentrations were significantly different among the three groups (OPCAB group < PMEA-coated group < heparin-coated group). The PMNE concentration was significantly lower in the OPCAB group and the heparin-coated group as compared to the PMEA-coated group both at the end of CPB and 4 hours after CPB. C3a concentration was significantly lower in the OPCAB group than in the CPB groups at the end of CPB. Clinical variables did not differ significantly among the three groups. CONCLUSION: Off-pump CABG is associated with a reduction in the inflammatory response when compared with on-pump CABG, using either PMEA-coated or heparin-coated circuits.     

Cardiopulmonary bypass elicits a pro- and anti-inflammatory cytokine response and impaired neutrophil chemotaxis in neonatal pigs

BACKGROUND: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response and organ dysfunction, especially in children. Plasma concentration of inflammatory markers are increased in response to the trauma of cardiac surgery and CPB. The aim of the present study was to investigate whether the CPB procedure in itself elicits increased levels of inflammatory markers in neonatal pigs. METHODS: The inflammatory response was measured in piglets undergoing sternotomy alone (sham group, n=13) or sternotomy and CPB (n=14). Inflammatory mediators were measured at baseline and at fixed time-points during and after CPB. IL-8, IL-10 and TNF-alpha levels and C-reactive protein (CRP) concentrations were measured in plasma samples. Polymorphonuclear neutrophils (PMN) chemotaxis was measured ex vivo, and CD-18 expression using an immunofluorescence technique. RESULTS: Immediately after the CPB procedure increased IL-8 levels were found in the CPB group, but not in sham operated animals (P=0.005). Simultaneously, a marked IL-10 response was measured in the CPB group. Concurrently, PMN chemotaxis decreased in CPB animals but not in the sham group (P=0.04). CD-18 expression and CRP levels were not significantly different between groups and TNF-alpha showed no changes in either group. The chemotactic response did not correlate with plasma IL-8 or IL-10, nor with CD-18 expression. CONCLUSION: The CPB procedure elicited a systemic inflammatory response in terms of significantly elevated plasma levels of IL-8 and IL-10. Furthermore, a temporary and simultaneous decrease in PMN chemotaxis was observed immediately after CPB.     

Biocompatibility of poly2methoxyethylacrylate coating for cardiopulmonary bypass.

The systemic inflammatory response to cardiopulmonary bypass (CPB) may contribute to the development of postoperative complications. Heparin-coated circuits and poly2methoxyethylacrylate (PMEA)-coated circuits have been developed to reduce the risk of such complications. We compared the biocompatibility of these circuits. Twelve patients scheduled to undergo elective coronary artery bypass grafting (CABG) with CPB were assigned to CPB with a PMEA-coated circuit (PMEA-coated group, n=6) or a heparin-coated circuit (heparin-coated group, n=6). The plasma concentrations of the following inflammatory markers were measured before CPB and just after, 4 hours after, and 24 hours after the termination of CPB: cytokines (interleukin [IL]-6, IL-8, IL-10), complement factor (C3a), polymorphonuclear elastase (PMNE), and coagulofibrinolytic factors (thrombin-antithrombin III complex [TAT], D-dimer). Postoperative clinical response was evaluated on the basis of respiratory index, blood loss, and the postoperative and preoperative body-weight percent ratio. There were no significant differences between the groups in the plasma concentrations of IL-6, IL-10, C3a, PMNE, TAT, or D-dimer. Plasma IL-8 concentrations were below the assay detection limits at all time points in both groups. Clinical variables did not differ significantly between the groups. In conclusion, PMEA-coated CPB circuits are as biocompatible as heparin-coated CPB circuits and prevent postoperative organ dysfunction in patients undergoing elective CABG with CPB.     

Inflammatory response in patients undergoing hip surgery due to osteoarthrosis or different types of hip fractures

OBJECTIVE: Hip surgery represents a major intervention associated with significant inflammatory response. The objective of our study was to compare markers of systemic inflammation and soluble adhesive molecules in patients undergoing elective hip replacement to those with hip fracture either intracapsular (IC) or extracapsular (EC). DESIGN: We included 65 consecutive patients undergoing hip surgery--17 patients with elective hip replacement (EL group), 29 patients with EC fracture (EC group) and 11 patients with IC fracture (IC group). Fibrinogen (FBG), orosomucoid (ORM), C-reactive protein (CRP), transferrin (TRF) and white blood cells count (WBC), sP-selectin, sE-selectin, and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before surgery 4h, 48h, and 7 days after surgery. RESULTS: IC patients had preoperatively highest values of inflammatory markers including FBG, CRP, ORM, WBC and lowest values of TRF, as compared to intermediate values found in EC and lowest values in EL groups. The surgery has led in all three subgroups to significant elevation in CRP, ORM and decrease in TRF. In IC group, the subsequent recovery of inflammatory markers was very slow. We noted a significant suppression of sP-selectin and sE-selectin values in all subgroups after surgery. The decrease of sE-selectin but not of sP-selectin correlated with changes in hemoglobin and blood transfusions' administration. CONCLUSIONS: Hip surgery is associated with significant inflammatory reaction. In patients with hip fractures, inflammatory markers are elevated already preoperatively, more so in IC than in EC fractures. The unexpected observation of a significant postoperative decrease in sE-selectin and sP-selectin will require further research for elucidation.     

Reduced complement activation during cardiopulmonary bypass does not affect the postoperative acute phase response.

OBJECTIVE: In the present study the relationship was evaluated between perioperative inflammation and the postoperative acute phase response in patients undergoing elective coronary artery bypass grafting (CABG) assisted by cardiopulmonary bypass (CPB). CPB circuits contained either non-coated- (UMS), Carmeda- (BPS) or Trillium-coated oxygenators (BAS). METHODS: Prospectively, 71 CABG patients were randomly allocated to one of the oxygenator groups (UMS: n=25, BPS: n=25 and BAS: n=21). Terminal complement complexes (TCC) and elastase were determined in plasma samples collected before, during and after bypass. Secretory phospholipase A2 (sPLA2) and C-reactive protein (CRP) were determined before and after bypass. RESULTS: Demographic, CPB and clinical outcome data were similar for the three groups. TCC and elastase increased during CPB, and decreased thereafter. Significant differences between the groups were present in the levels of TCC at the end of CPB (P=0.002) and at the first (P=0.012) and second (P<0.001) postoperative days, the BPS and BAS groups having reduced levels of TCC compared to the UMS group. Also elastase concentrations differed significantly between the groups at the end of CPB (P<0.001). The postoperative sPLA2 and CRP levels increased in all three groups on the first and second postoperative days, but no significant differences were present between the groups. CONCLUSIONS: Material-induced reduction of the inflammatory response during CPB does not affect the postoperative acute phase response. Thus, in CABG patients this response seems relatively unaffected by the composition and/or biocompatibility of the modern CPB circuit and rather to be evoked by surgical trauma, anesthetics and organ perfusion.     

Expression of adhesion molecules and cytokines after coronary artery bypass grafting during normothermic and hypothermic cardiac arrest

Objective: Cardiac surgery with cardiopulmonary bypass (CPB) results in vascular injury and tissue damage which involves leukocyte-endothelial interactions mediated by cytokines and adhesion molecules. This study was designed to demonstrate the effect of normothermic and hypothermic CPB to cytokine and soluble adhesion molecule levels in adults and to determine whether these levels correlate to the patients postoperative course. Design and patients: In 25 patients after normothermic and in 25 patients after hypothermic coronary artery bypass grafting with cardiopulmonary bypass (CPB), blood samples for cytokine and soluble adhesion molecule analysis were taken preoperatively, 24, 36, 48 h, and 6 days postoperatively. Soluble adhesion molecules (sE-selectin, sICAM-1) were measured by ELISA and cytokines (TNF-, IL-6, IL-8) by chemilumenscent-immunoassay. Clinical data were collected prospectively. Results: Postoperatively, adhesion molecule and cytokine levels were significantly elevated after CPB. Mean plasma levels of sICAM-1 was 2.4-fold higher after 6 days. Mean plasma concentration of sE-selectin peaked after 48 h with a 2-fold increase compared to normothermic conditions. In the hypothermia group sICAM-1, sE-selectin, IL-6, and IL-8 showed significantly higher levels (P<0.0057, P<0.0012, P<0.0419, P<0.0145) after 24 h compared to the normothermia group. No clinical differences were seen. Conclusion: Adhesion molecules and cytokines are elevated after CPB. Patients after hypothermic CPB show significant higher sICAM-1, sE-selectin, IL-6, and IL-8 levels after 24 h compared to normothermic conditions. These results are mainly due to longer CPB and crossclamp times but do not alter the patient's postoperative course.     

Cerebral inflammatory response during and after cardiac surgery

BACKGROUND AND OBJECTIVE: Neurological dysfunction is a common problem after cardiac surgery with cardiopulmonary bypass (CPB). Cerebral ischaemia associated with the use of CPB may result in a release of neuronal-ischaemic markers and a subsequent cerebral inflammatory response which may additionally release inflammatory cytokines. In order to locate the origin and to quantify the release of neuronal-ischaemic markers and cytokines we investigated arterial-cerebral venous concentration gradients during and after CPB in a clinical setting. METHODS: In twenty-five patients scheduled for coronary artery bypass grafting surgery we measured the plasma concentration of neuron-specific enolase, S-100beta protein as well as interleukins (IL) IL-6, IL-8 and IL-10 from arterial and cerebral venous blood samples prior to surgery (baseline), during hypothermic CPB at 32 degrees C, after termination of bypass, as well as 2, 4 and 6 h after admission to the intensive care unit. RESULTS: Arterial-cerebral venous concentration gradients of neuron-specific enolase, S-100beta, IL-6, IL-8 and IL-10 were neither detectable during nor after CPB. Compared to the baseline period, S-100beta and neuron-specific enolase significantly increased during hypothermic CPB. After termination of CPB, neuronal-ischaemic markers as well as cytokines were increased and remained elevated during the investigated time course without reaching baseline values. CONCLUSIONS: Although we found an overall increase in plasma concentrations of neuronal-ischaemic markers, IL-6, IL-8 and IL-10 during and after CPB, arterial-cerebral venous gradients were not detectable for any of these parameters. Our results suggest that the increase of investigated parameters associated with the use of CPB are not primarily caused by a cerebral inflammatory response but rather reflect a release from other sources in the systemic circulation.     

Respiratory dysfunction after cardiac surgery: effects of avoiding cardiopulmonary bypass and the use of bilateral internal mammary arteries.

BACKGROUND: The quantitative contribution of cardiopulmonary bypass (CPB) to respiratory dysfunction after cardiac surgery is not documented and the effect of the use of bilateral internal mammary artery (IMA) grafts is not clear. METHODS: One hundred and seventy-five patients undergoing CABG with (CPB, n=150) and without (NOCPB, n=25) CPB were studied. PMN elastase (as a marker of the systemic inflammatory response) and serial arterial oxygen (paO(2)) and carbon dioxide (paCO(2)) tension, alveolar arterial oxygen (AaO(2)) gradient and percent saturation were measured. The CPB group was subdivided into three groups by the number of IMA grafts used: 0IMA (n=12), 1IMA (n=82) and 2IMA (n=51). RESULTS: The NOCPB group was younger, had significantly better preoperative blood gases, received fewer grafts and had lower PMN elastase levels than the CPB group. In both groups maximum respiratory dysfunction occurred at 48 h (paO(2), percentage saturation and Aa gradient all P<0.001 versus baseline) with partial recovery by 5 days. The percentage decline and subsequent recovery in all blood gas parameters was near identical in the CPB and NOCPB groups. Amongst the three IMA groups the percentage changes in all blood gas parameters were similar, as was the duration of postoperative ventilation and time to discharge. There was no correlation between blood gas parameters at 48 h with age, CPB time, blood loss, duration of ventilation or peak PMN elastase level. CONCLUSIONS: Changes in postoperative gas exchange are similar in patients undergoing CABG with and without CPB even although PMN elastase levels indicate that CPB produces a more marked inflammatory response. The use of 2IMA compared with 1IMA does not increase respiratory dysfunction.     

Plasma nitrate/nitrite (NOx) is not a useful biomarker to predict inherent cardiopulmonary bypass inflammatory response

BACKGROUND AND AIM: There were strong evidences that nitric oxide has capital importance in the progressive vasodilatation associated with varied circulatory shock forms, including systemic inflammatory response syndrome (SIRS), in patients undergoing cardiac surgeries for cardiopulmonary bypass (CPB). If CPB procedures, per se, are the inciting stimulus for inflammation, plasma nitrate/nitrite (NOx) excretion would be expected to be higher in these patients rather than in patients operated without CPB. In consequence, we hypothesized that increased levels of NOx would be predictive for vasoplegic syndrome. METHODS: Thirty patients were assigned to three groups: Group 1--coronary artery bypass graft (CABG) roller pump CPB; Group 2--CABG centrifugal vortex pump CPB; and Group 3--heart valve surgery roller pump CPB. Sampling of venous blood for chemiluminescence plasma NOx dosage was achieved at the following time points: (1) before anesthesia induction; (2) after anesthesia induction; (3) before heparin infusion; (4) after heparin infusion; (5) CPB-30 minutes; (6) CPB-60 minutes; (7) before protamine infusion; (8) after protamine infusion; and (9) on return to the recovery area. RESULTS: There were no intergroup differences regarding age and anesthetic regimen, and the number of arteries grafted was not different between the CABG groups. There were no NOx statistic differences, neither among the three groups of patients or among the surgery time. In addition, there was no correlation among NOx, lactate, and hemoglobin. CONCLUSIONS: Considering the inflammatory process intrinsic to CPB, this study reinforces the idea that plasma NOx is not useful as a biomarker of inflammatory response onset, which may or may not lead to SIRS and/or vasoplegic syndrome.     

Carbon Monoxide Inhalation Reduces Pulmonary Inflammatory Response during Cardiopulmonary Bypass in Pigs

Background: Cardiopulmonary bypass (CPB) is associated with pulmonary inflammation and dysfunction. This may lead to acute lung injury and acute respiratory distress syndrome with increased morbidity and mortality. The authors hypothesized that inhaled carbon monoxide before initiation of CPB would reduce inflammatory response in the lungs.

Methods: In a porcine model, a beating-heart CPB was used. The animals were either randomized to a control group, to standard CPB, or to CPB plus carbon monoxide. In the latter group, lungs were ventilated with 250 ppm inhaled carbon monoxide in addition to standard ventilation before CPB. Lung tissue samples were obtained at various time points, and pulmonary cytokine levels were determined.

Results: Hemodynamic parameters were largely unaffected by CPB or carbon monoxide inhalation. There were no significant differences in cytokine expression in mononuclear cells between the groups throughout the experimental time course. Compared with standard CPB animals, carbon monoxide significantly suppresses tumor necrosis factor-[alpha] and interleukin-1[beta] levels (P < 0.05) and induced the antiinflammatory cytokine interleukin 10 (P < 0.001). Carbon monoxide inhalation modulates effector caspase activity in lung tissue during CPB.