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.     

Thrombin Generation During Cardiopulmonary Bypass Using Heparin-Coated or Standard Circuits

For quantitative comparison of thrombin generation during cardiopulmonary bypass (CPB) with heparin-coated vs conventional CPB circuits, thrombin-antithrombin III complex (TAT) and prothrombin fragment 1+2 (F₁₊₂) were analyzed in 20 patients undergoing combined heart valve surgery and coronary artery bypass grafting (CABG), in ten cases with heparin-coated circuits (COMB-HC) and in ten with standard circuits (COMB-C). Extensive thrombin generation was found in both groups, with maximal TAT and F₁₊₂ levels at the end of CPB. Of 15 operations with only CABG, seven were performed with heparin-coated circuits and heparin dose 40% of normal (CABG-HC), and eight with standard circuits and normal heparin doses (CABG-C). TAT was maximal at the end of CPB and F₁₊₂ peaked 3 hours after protamine injection. At the end of CPB both levels were significantly higher in the CABG-HC than in the CABG-C group, though thrombin generation was less than in the COMB groups. The abundant thrombin generation during CPB thus was much more pronounced during complex operations. Use of heparin-coated circuits did not reduce thrombin generation, which was increased by 60% reduction of the systemic heparin dose. The clinical implications are still unknown, as no complications were observed.     

Biocompatibility of Heparin-Coated Circuits in Pediatric Cardiopulmonary Bypass

Abstract: In this study, we evaluated the biocompatibility of heparin-coated circuits in pediatric cardiopulmonary bypass (CPB). Eight patients were divided into 2 groups: the control group (Group C) and heparin-coated group (Group H). In Group H, CPB circuits, including the arterial pump, oxygenator, and cannulas were heparin-coated. Before, during, and after CPB, blood samples were obtained to assess the platelet counts (Plat), α2-plasmin plas-minogen inhibitor complex (PIC), thrombin-antithrombin III complex (TAT), C3 activation products (C3a), inter-leukin (IL)-6, IL-8, and polymorphonuclear neutrophil leukocyte (PMN) elastase. There was no significant difference in Plat, PIC, or TAT between groups. Group H showed significantly low levels of C3a (during and after CPB), PMN elastase (during CPB), and IL-6 (after CPB). These data demonstrated that in pediatric CPB, heparin-coated CPB circuits reduced the activation of complements and the production of PMN elastase and IL-6, suggesting the superior biocompatibility of the heparin-coated circuits.     

Biocompatibility of heparin-coated cardiopulmonary bypass circuits in coronary patients with left ventricular dysfunction is superior to PMEA-coated circuits

BACKGROUND: Several coating techniques for extracorporeal circulation have been developed to diminish the systemic inflammatory response during cardiopulmonary bypass (CPB). The aim of this study was to evaluate the clinical effectiveness and biocompatibility of heparin-coated and poly-2-methoxyethylacrylate (PMEA)-coated CPB circuits on coronary patients with left ventricular systolic dysfunction. METHODS: Thirty-six patients who underwent elective coronary artery bypass grafting were divided into two equal groups: group H (n = 18), heparin-coated; group P (n = 18), PMEA coated. Clinical outcomes, hematologic variables, cardiac enzymes, malondialdehyde (MDA), and acute phase inflammatory response (including myeloperoxidase (MPO), catalase, hsCRP, and IL-8) were analyzed perioperatively. RESULTS: Demographic, CPB, and clinical outcome data were similar for both groups. Plasma fibrinogen, total protein, albumin, and platelet count decreased, neutrophil count, MDA, IL-8, MPO, and catalase levels increased during CPB. During CPB, MPO and catalase values were significantly higher in group P (p = 0.02 and p = 0.01) and postoperative MDA concentration was lower in group H (p = 0.03). Platelet counts were better preserved in group H during and after CPB but neutrophil count and IL-8 level did not differ between the groups. Postoperative total protein, albumin, and fibrinogen levels were higher in group H (p < 0.05). The postoperative first day levels of troponin-I, CK-MB, and CRP increased in both groups without any significant differences between the groups. CONCLUSIONS: Heparin-coated circuit provided better suppression of perioperative inflammatory markers and exhibited more favorable effects on hematologic variables than PMEA-coated circuit.     

A new poly-2-methoxyethylacrylate-coated cardiopulmonary bypass circuit possesses superior platelet preservation and inflammatory suppression efficacy

BACKGROUND: Poly-2-methoxyethylacrylate (PMEA) is a new coating material, and several studies have revealed that PMEA-coated cardiopulmonary bypass (CPB) circuits have good biocompatibility. This study sought to compare this biocompatibility with those of heparin-coated and noncoated circuits. METHODS: Forty-five patients undergoing coronary artery bypass grafting were randomly assigned to PMEA-coated (group P, n = 15), heparin-coated (group H, n = 15), or noncoated (group N, n = 15) circuit groups. Clinical data and the following markers were analyzed: (1) platelet preservation by number of platelets; (2) complement (C) activation by C3a and C4a levels; (3) inflammatory response by interleukin-6 (IL-6) and interleukin-8 (IL-8) levels. RESULTS: Platelet numbers were significantly preserved in group P compared with groups N and H. Postoperative blood loss did not differ among the groups. During CPB, C3a values were significantly lower in group H (536 +/- 145 ng/mL) than in group P (1,458 +/- 433 ng/mL, p < 0.01) and group N (1,815 +/- 845 ng/mL, p < 0.01). The C4a values did not differ 60 minutes after CPB initiation among the groups. The IL-6 and IL-8 levels were significantly lower in group P and group H than in group N. CONCLUSIONS: The PMEA coating was superior to heparin coating and noncoating in preserving platelets, and was equivalent to heparin coating in terms of the perioperative clinical course and inhibition of inflammatory cytokines, but slightly inferior in reducing complement activation.     

Cytokine release and neutrophil activation are not prevented by heparin-coated circuits and aprotinin administration

BACKGROUND: Cardiopulmonary bypass (CPB) initiates a whole-body inflammatory response where complement and neutrophil activation and cytokine release play an important role. This prospective trial examined the effects of both heparin-coated circuits and aprotinin on the inflammatory processes during CPB, with respect to cytokine release and neutrophil activation. METHODS: Two hundred patients undergoing cardiac surgery were randomized in four groups of 50 patients each: heparin-coated circuit with aprotinin (HCO-A) or without aprotinin (HCO) administration, and uncoated circuit with aprotinin (C-A) or without aprotinin administration (C). In groups receiving aprotinin, a high-dose regimen was given. In all groups, high initial doses of heparin were used (3 mg/kg intravenously). Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-8, and myeloperoxidase and elastase levels were measured in plasma samples taken before, during, and after CPB. RESULTS: In all groups, the TNF-alpha, IL-6, and IL-8 levels reached a maximum after protamine administration. After 24 hours, they remained significantly elevated (IL-6 and IL-8) or returned to baseline values (TNF-alpha). A similar pattern was observed with myeloperoxidase and elastase levels. No significant intergroup differences were observed. CONCLUSIONS: CPB is associated with cytokine release and neutrophil activation, which are not attenuated by the use of heparin-coated circuits or by the administration of aprotinin. Aprotinin and heparin-coated circuits do not show additive effects.     

Circulating Cytokines and Granulocyte-Derived Enzymes During Complex Heart Surgery: A Clinical Study with Special Reference to Heparin-Coating of Cardiopulmonary Bypass Circuits

Blood contact with artificial surfaces during cardiopulmonary bypass (CPB) triggers a systemic inflammatory response in which complement, granulocytes and cytokines play a major role. Heparin-coated CPB circuits were recently shown to reduce complement and granulocyte activation in such circumstances. The present study comprised 20 complex heart operations, 10 with heparin-coated circuits (group HC) and 10 controls (group C), with evaluation of changes in terminal complement complex, the granulocyte enzymes myeloperoxidase and lactoferrin, and the cytokines interleukin-6 (IL-6) and interleukin-8 (IL-8). Standard heparin dose and uncoated cardiotomy reservoir were used in all cases. In both groups the levels of enzymes and terminal complement complex rose significantly, beginning at conclusion of CPB, above base values, without significant intergroup differences. IL-6 and IL-8 also increased significantly, but tended to be lower in the HC group, starting at CPB end and continuing until 20 hours postoperatively: for IL-6 the difference was significant at CPB end (83 ± 18 vs 197 ± 39 μg/1, p = 0.21). Significantly increased inflammatory response was thus found during complex heart operations even with use of heparin-coated CPB sets. The heparin-coating of circuits seems to diminish cytokine production.     

Effects of poly-2-methoxyethylacrylate (PMEA)-coating on CPB circuits

OBJECTIVES: In this study, the immuno- and neuroprotective effect of a novel cardiopulmonary bypass coating was investigated. DESIGN: Thirty nine patients scheduled for elective coronary artery bypass grafting were randomly assigned to either PMEA-coated (n = 19) or non-coated CPB circuits (n = 20). Pericardial suction blood was separated and retransfused only if needed at the end of operation. Neurocognitive functions were examined preoperatively and 7-10 days postoperatively using a standard neuropsychological test battery. Assuming an inflammatory etiology, the most cogent inflammatory markers were perioperatively analyzed. RESULTS: Postoperatively, patients of the PMEA-coated group performed better in Go/NoGo and Mini-Mental-test than patients of the non-coated group (p < 0.04). Other neurocognitive testing did not reveal significant differences between the groups. Although most inflammatory parameters showed a significant intraindividual increase during or shortly after CPB, there was no difference in inflammatory alteration between the groups. CONCLUSIONS: PMEA-coating of cardiopulmonary bypass surfaces revealed some minor benefits in preservation of neurocognitive functions after surgery. The immediate inflammatory response remained mostly unaffected. Suction blood separation may additionally contribute to proper postoperative outcome.     

Effects of urinary protease inhibitor on inflammatory response during on-pump coronary revascularisation. Effect of ulinastatin on inflammatory response

AIM: Cardiac surgery in patients undergoing cardiopulmonary bypass (CPB) provokes a vigorous inflammatory response with substantial clinical implications. Once the inflammatory response is triggered by CPB, leukocytes and platelets are activated by multiple stimuli. The administration of a urinary trypsin inhibitor (ulinastatin) during CPB is hypothesized to reduce cytokine release and platelet activation and to decrease pulmonary injury. We performed a prospective randomized study to investigate the influence of high-dose ulinastatin on cytokines and platelet activation and on respiratory function during and after CPB. METHODS: In this pilot, prospective, randomized and double-blinded study, 30 first-time three-vessel coronary artery disease (CAD) patients undergoing coronary artery bypass graft (CABG) were randomly divided into 2 groups: U group (n=15) received a total dose of 1000000 U ulinastatin and C group (n=15) received placebo. Blood samples were withdrawn from the central vein to measure polymorphonuclear neutrophil elastase (PMNE), tumour necrosis factor-alpha (TNF-a), interleukin-6 (IL-6) and interleukin-8 (IL-8), before induction, 30 min following clamping (T2), reperfusion 3 h (T3), reperfusion 6 h (T4) and reperfusion 12 h (T5). Whole blood samples were taken for CD62P immediately before induction (as baseline), at the end of CPB (before protamine administration), 1 h after heparin neutralization by protamine and 24 h after the operation. In addition, alveolo-arterial oxygen difference (A-aDO(2)) in pulmonary gas exchange function was calculated by obtaining arterial blood gas samples before and after CPB. RESULTS: There were no differences in preoperative parameters between the groups. After CPB, the levels of PMNE, TNF-alfa, IL-6 and IL-8 increased in both groups over baseline values (P<0.01). The levels of PMNE, TNF-alfa, IL-6 and IL-8 in U group were significantly lower than those in C group (P<0.05). No significant differences in CD62p expression between the 2 groups during CPB were found. A-aDO(2) in U group significantly decreased compared with C group (P<0.05) and the duration of mechanical ventilation was shorter than C group (P<0.05). CONCLUSION: Results suggest that ulinastatin may inhibit proinflammatory cytokine (PMNE, TNF-alfa, IL-6 and IL-8) release, reduce reperfusion lung injury and preserve pulmonary function but it fails to inhibit platelet activation and to prevent blood loss during CPB.     

Heparin-bonded cardiopulmonary bypass circuits reduce cognitive dysfunction

OBJECTIVE: To determine the incidence of cerebral dysfunction in cardiac surgical patients exposed to heparin-bonded cardiopulmonary bypass (HB-CPB) versus nonheparin-bonded cardiopulmonary bypass (NH-CPB) circuits through neuropsychometric testing and to correlate these findings with markers of the systemic inflammatory response to CPB. DESIGN: Prospective, randomized, blinded clinical trial. SETTING: University hospital. PARTICIPANTS: Sixty-one patients undergoing elective cardiac surgery. INTERVENTIONS: A cohort of 61 patients scheduled for elective coronary artery bypass graft surgery were prospectively randomized to receive either HB-CPB or NH-CPB circuits during surgery. Patients were evaluated for cerebral injury using a battery of neuropsychometric tests at the following 3 time points: (1) before surgery as a baseline examination, (2) postoperative day 5, and (3) postoperative week 6. Blood samples were drawn to measure inflammatory markers at the following time points: (1) preincision, after induction of anesthesia, (2) 15 minutes after onset of CPB, (3) 30 minutes after CPB, (4) 6 hours postoperatively, and (5) 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS: Neuropsychometric performance was evaluated by group-rate and event-rate analyses. By group-rate analysis, patients undergoing surgery with HB-CPB performed significantly better at 5 days after surgery on 2 neuropsychometric tests (trails A [p < 0.01] and finger tapping with the dominant hand [p < 0.01]) and at 6 weeks after surgery on one neuropsychometric test (trails A [p < 0.01]). By event-rate analysis, at 5 days, patients undergoing surgery with HB-CPB circuits had less cognitive dysfunction (p < 0.05) compared with patients undergoing surgery with NH-CPB circuits. Serum samples were analyzed to evaluate markers of complement activation (C3a), proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6), and coagulation (thrombin-antithrombin complex [TAT]) using the quantitative sandwich enzyme immunoassay technique. Although there were no significant differences in cytokine activation in either group, C3a was significantly higher in the NH-CPB group intraoperatively at 1 hour after CPB (p < 0.05), and TAT was higher in the HB-CPB group at 24 hours after surgery (p < 0.05). CONCLUSIONS: Patients undergoing cardiac surgery with CPB have less postoperative cognitive dysfunction during CPB when HB-CPB circuits are employed. Although there was a relationship, this finding did not correlate with decreased complement activation intraoperatively and activation of coagulation postoperatively.     

Influence of PMEA-coated bypass circuits on perioperative inflammatory response

BACKGROUND: Poly(2-methoxyethylacrylate) (PMEA) is a new coating material, and several experimental studies have revealed excellent biocompatibility of PMEA-coated cardiopulmonary bypass circuits. The clinical utility of the PMEA-coated circuits was compared with that of uncoated circuits, focusing on perioperative inflammatory response. METHODS: Twenty-two patients were randomized to PMEA-coated (group P; Capiox RX25; n = 11) or uncoated (group U; Capiox SX10; n = 11) circuit group, and underwent coronary artery bypass grafting and/or valve operations. The following markers, as well as clinical outcomes, were analyzed perioperatively: (a) complement activation by C3a (including C3a-desArg) concentrations; (b) leukocyte activation by polymorphonuclear-elastase concentrations; (c) acute phase inflammatory response by interleukin-6 concentrations; and (d) platelet preservation by number of platelets. RESULTS: The maximal values of C3a and polymorphonuclear-elastase were significantly lower in group P than in group U. The intergroup difference of interleukin-6 was not significant. Although preservation of platelets was significantly better in group P until 1 hour after initiating cardiopulmonary bypass, no significant intergroup difference was observed thereafter. The duration of postoperative mechanical ventilation revealed no significant intergroup difference. CONCLUSIONS: The PMEA-coated circuits exhibited better suppression of perioperative complement and leukocyte activation than the uncoated circuits. In addition, the price of the PMEA-coated circuits is the same as that of the uncoated circuits. Therefore, we judged that the clinical utility of the PMEA-coated circuits is superior to those of the uncoated circuits.     

Heparin-coated Cardiopulmonary Bypass Circuits in Coronary Bypass Surgery

Abstract: Cardiopulmonary bypass (CPB) is a nonphysiologic environment for an organism. The damage of blood components may also lead to organ dysfunction, sometimes recognized as postperfusion syndrome. One possible way to diminish the risk of these complications would be to reduce the thorombogenicity and to improve the biocompatibility of the artificial surfaces by using a heparin-coated CPB circuit. In this study, we compared a heparin-coated CPB circuit with a noncoated CPB circuit in terms of biocompatibility in 20 patients undergoing elective coronary bypass surgery. We employed a Dura-flo II (n = 10) as a heparin-coated CPB circuit and a Univox IC (n = 10) as control subjects. Ten patients (Group C) were operated on using the heparin-coated CPB circuit. A total of 10 patients were given heparin in a reduced dose (2.0 mg/kg), and additional heparin was given if the activated clotting time (ACT) was below 400 s. The control group also included 10 patients (Group NC), who were operated on with noncoated devices. They received 2.5 mg/kg of heparin, and additional heparin was given if the ACT was below 450 s. All patients had normal coagulation parameters and did not receive blood transfusion. We measured complement activation levels (C3a, C4a), platelet count, thrombin-antithrombin III complex levels, D-dimer levels, and ACT during CPB and respiratory index postoperatively. The concentration of C3a in group NC was significantly higher than that in group C. Platelet reduction in group NC was significantly greater than that in group C. There were no significant differences in the remaining parameters between the 2 groups. We concluded that heparin-coated CPB circuits improved biocompatibility by reducing complement activation and platelet consumption and enabled us to reduce the dose of heparin required for systemic heparinization.     

Effect of polymer coating (poly 2-methoxyethylacrylate) of the oxygenator on hemostatic markers during cardiopulmonary bypass in children

OBJECTIVE: Heparin and other oxygenator coatings have been used in attempts to reduce hemostatic activation during cardiopulmonary bypass (CPB). This study evaluated whether an oxygenator coated with poly 2-methoxyethylacrylate (PMEA) (X-coating; Terumo Corporation, Tokyo, Japan) would cause less activation of coagulation and fibrinolytic systems during CPB in children than a noncoated oxygenator. DESIGN: Observational study. SETTING: University-affiliated children's hospital. PATIENTS: Twenty-six patients, 3 months to 5 years old, who underwent congenital heart surgery for repair of a ventricular septal defect, atrial septal defect, or both. INTERVENTIONS: Patients were divided into 2 age-matched groups based on the type of oxygenator used: a noncoated oxygenator (group NC) versus a PMEA-coated oxygenator (group C). MEASUREMENTS AND MAIN RESULTS: Blood samples for coagulation and fibrinolytic markers were compared before, during, and after CPB. Despite increases in thrombin generation markers (F1.2 and TAT) at certain times during CPB in group C compared to group NC, a comparison over all times during CPB were not statistically different between groups. Overall D-dimer concentrations during CPB were elevated in group C compared to group NC (p = 0.02). Active tPA and active PAI-1 were not different between groups during or after CPB. Group C had higher platelet counts (181,000 +/- 29,000) during CPB than group NC (155,000 +/- 57,000, p = 0.04) but not postoperatively. Twelve hours postoperatively, chest tube outputs were 8.8 +/- 3 mL/kg in group C and 19.1 +/- 12 mL/kg in group NC (p = 0.003). The corresponding outputs 24 hours after surgery were 12.4 +/- 3 mL/kg and 24 +/- 11 mL/kg, respectively (p = 0.005). CONCLUSIONS: Except for a somewhat higher platelet count during CPB, there was no indication that PMEA coating resulted in less activation of coagulation and fibrinolytic systems. The lower postoperative chest tube output observed after CPB with PMEA-coated oxygenators needs to be studied further.     

Off-pump CABG reduces complement activation but does not significantly affect peripheral endothelial function: a prospective randomized study

OBJECTIVE--Cardiac surgery initiates a systemic inflammatory response, which may affect endothelial function. The aim of this study was to investigate if off-pump CABG (OPCAB) reduces the postoperative inflammatory response and affects endothelial function less than conventional on-pump CABG. DESIGN--Fifty-two patients submitted for elective CABG were included in a prospective, randomized study. Twenty-six patients were operated with, and 26 without cardiopulmonary bypass (CPB). Plasma levels of complement (C3a), cytokines (IL-8, TNF-alpha), endothelin-1 and neopterin were measured before and during surgery and 2 and 24 h after surgery. Endothelial function was assessed by forearm plethysmography and acetylcholine infusion in 30 patients 2-4 h after surgery. RESULTS--C3a and neopterin concentrations were significantly higher during and early after surgery in the CPB group while TNF-alpha and IL-8 tended to be higher in the CPB group but the difference did not reach statistical significance. Endothelial function did not differ significantly between the two groups. CONCLUSION--OPCAB reduces complement activation compared with on-pump CABG but does not significantly affect TNF-alpha and IL-8 release or endothelial function.     

Effects of poly-2-methoxyethylacrylate (PMEA)-coating on CPB circuits

Objectives. In this study, the immuno- and neuroprotective effect of a novel cardiopulmonary bypass coating was investigated. Design. Thirty nine patients scheduled for elective coronary artery bypass grafting were randomly assigned to either PMEA-coated (n?=?19) or non-coated CPB circuits (n?=?20). Pericardial suction blood was separated and retransfused only if needed at the end of operation. Neurocognitive functions were examined preoperatively and 7–10 days postoperatively using a standard neuropsychological test battery. Assuming an inflammatory etiology, the most cogent inflammatory markers were perioperatively analyzed. Results. Postoperatively, patients of the PMEA-coated group performed better in Go/NoGo and Mini-Mental-test than patients of the non-coated group (p?<?0.04). Other neurocognitive testing did not reveal significant differences between the groups. Although most inflammatory parameters showed a significant intraindividual increase during or shortly after CPB, there was no difference in inflammatory alteration between the groups. Conclusions. PMEA-coating of cardiopulmonary bypass surfaces revealed some minor benefits in preservation of neurocognitive functions after surgery. The immediate inflammatory response remained mostly unaffected. Suction blood separation may additionally contribute to proper postoperative outcome.     

Effects of new polymer-coated extracorporeal circuits on biocompatibility during cardiopulmonary bypass

An inflammatory response due to bioincompatibility of extracorporeal circuits is a major clinical issue during cardiopulmonary bypass (CPB). By using a swine model, we determined whether new polymer-coated circuits, the blood-contacting surfaces of which are coated with poly(2-methoxyethylacrylate) (PMEA), would reduce the inflammatory response during CPB. Plasma bradykinin levels and the percentages of CD35-positive monocytes in PMEA-coated circuits were significantly lower than those in uncoated circuits during CPB. The amount of proteins adsorbed on the PMEA-coated circuits was significantly lower than that on the uncoated circuits (0.30 microg/cm2 versus 3.42 microg/ cm2). Almost no IgG, IgM, or C3c/d was detected in proteins adsorbed on the PMEA-coated circuits although these proteins were clearly detected in proteins adsorbed on the uncoated circuits. We concluded that PMEA coating could reduce complement activation during CPB by suppressing the adsorption of IgG and IgM, which activate C3 via the classical pathway, on the surface of the circuits.     

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.     

Heparin-coated cardiopulmonary bypass circuits reduce blood cell trauma. Experiments in the pig

Blood cell trauma and postoperative bleeding remain important problems in cardiopulmonary bypass (CPB). We compared heparin-coated with non-coated circuits in the pig. Twenty animals were perfused for 2 h at normothermia using membrane oxygenators (Bentley Bos 50). Two groups were studied. In the non-coated group (NC, n = 11) the CPB circuits used were without a heparin coating. This group had systemic heparinization of 400 IU/kg to maintain an ACT (activated clotting time) of over 400 s during CPB. In the coated group (C, n = 9), all surfaces exposed to blood in the CPB circuits were heparin-coated. This group had the heparin dose reduced to 25% (100 IU/kg) without further administration regardless of ACT. During CPB, group C displayed shorter ACT (per definition), higher platelet count, platelet adhesion and lower fibrinolysis and haemolysis (P less than 0.05) as compared to group NC. No thromboembolic events were detected during CPB. Three animals in group NC and 4 animals in group C were weaned from CPB and protaminized. Four hours postoperatively, the leucocyte consumption was two-fold greater and blood loss about four-fold greater in group NC as compared with group C (P less than 0.05). Perfusion with heparin-coated surfaces reduces blood cell trauma. The decreased postoperative blood loss observed in group C is probably explained by the reduced dosages of heparin and protamine.     

The release of systemic inflammatory mediators is independent of cardiopulmonary bypass temperature

OBJECTIVE: The aim of this study was to investigate the effect of systemic CPB temperature on the production of the key mediators of the systemic inflammatory response to coronary artery bypass graft (CABG) surgery. DESIGN: Randomized clinical study. SETTING: University hospital. PARTICIPANTS: Thirty patients undergoing first-time CABG surgery. INTERVENTIONS: The patients were randomized to hypothermic (32 degrees C, n = 15) or normothermic (36 degrees C, n = 15) CPB. MEASUREMENTS AND MAIN RESULTS: Plasma interleukin (IL)-6, IL-8, IL-10, C-reactive protein (CRP), cortisol, and neutrophils were measured the day before operation, at closure of the sternum, and 4, 16, and 44 hours later. The cytokine, CRP, cortisol, and neutrophil responses were independent of temperature during CPB with peak concentrations of IL-10 at closure of the sternum followed by IL-6, IL-8, cortisol, neutrophils, and finally CRP. A correlation between maximal plasma concentrations of IL-10 and cortisol was seen in both groups after surgery (p = 0.02). Drainage after surgery was lower after normothermic CPB (p=0.02), with no difference in the requirement for blood transfusion. All patients were discharged from the intensive care unit within 24 hours after surgery. CONCLUSIONS: The release of systemic inflammatory mediators after cardiac surgery was independent of mild hypothermia (32 degrees C) versus normothermia (36 degrees C) during CPB.