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.     

Biocompatibility of heparin-coated extracorporeal bypass circuits: new heparin bonded bioline system

Biocompatibility of a new type of heparin-coated cardiopulmonary bypass equipment, the Bioline, was evaluated in coronary artery bypass surgery cases. The heparin-coated (H) group (n = 15; Quadrox Bioline oxygenator/reservior and Carmeda BioMedicus BP-80 centrifugal pump) was compared with the nonheparin-coated (N) group (n = 12; uncoated, otherwise similar oxygenator, centrifugal pump, tubing, and filter set). Both groups used full systemic heparinization. The peak values of neutrophil elastase, C3a, IL-6, and IL-8 at 2 h after cardiopulmonary bypass (CPB), and C3a levels at the end of CPB and at 2 h after CPB were significantly reduced in the H group compared with those of the N group. However, no statistically significant intergroup differences were observed in thrombin-antithrombin complex, D-dimer, beta-thromboglobulin, or platelet factor-4. No significant differences were observed in hemostasis time, postoperative 12 h blood loss, required amount of blood transfusion, or intubation time. In conclusion, the Bioline demonstrated partially improved biocompatibility, in terms of leukocyte and complement activation, and proinflammatory cytokine production. However, it did not improve platelet activation, coagulation, or fibrinolysis cascade under full systemic heparinization. As a result, the clinical beneficial impact seemed to be the minimum.     

Safety of heparin-coated circuits in primates during deep hypothermic cardiopulmonary bypass

The purpose of this study is to evaluate the biologic impact of heparin-coated circuits without systemic heparinization during deep hypothermia. Baboons (n=6) were placed on a heparin-coated pediatric closed-circuit cardiopulmonary bypass (CPB) system and cooled to 18 degrees C. A control group (n=7) underwent similar protocol with a non heparin-coated circuit and received systemic heparin. Either low flow at 0.5 L/min/m 2 (n=8; 4 in each group) or circulatory arrest (n=5; 2 in experimental group and 3 in control group) was used during deep hypothermia. Samples for complete blood count (CBC), hepatic and renal function tests, activated clotting time (ACT) and thrombelastogram (TEG) were obtained before, during, and after bypass. Cerebral blood flow was measured using Xenon-133 and autopsies were performed to assess end-organ damage. The ACT returned to baseline in both groups, and renal and hepatic function were within normal limits. There was no significant difference between the TEG values between the groups post bypass. Fibrin split products were absent and fibrinogen levels were normal in both groups following bypass. Cerebral blood flows were equivalent in both groups before and after bypass, although in the heparin-coated group cerebral blood flows were significantly higher during CPB. There were no brain histologic changes in the heparin-coated group and one focal cortical infarct in the control group. This study suggests that hypothermia induced a state of anticoagulation that did not result in thrombus formation or end organ dysfunction during CPB with a heparin-coated circuit.(ABSTRACT TRUNCATED AT 250 WORDS)     

Changes in Platelet, Granulocyte, and Complement Activation During Cardiopulmonary Bypass Using Heparin-coated Equipment

Abstract: The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 ± 632 ng/ml) and C4a (1088 ± 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 ± 1045 ng/ml and 1494 ± 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 ± 177 μg/L) and 10 min after the administration of protamine (676 ± 314 μg/L) were significantly (p < 0.05) lower than in the other 2 groups (820 ± 341 and 893 ± 303 μg/L and 1365 ± 595 and 1,258 ± 622 μg/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma β-throm-boglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.     

A prospective,double-blind study on the efficacy of the bioline surface-heparinized extracorporeal perfusion circuit

BACKGROUND: We evaluated the newly introduced Bioline heparin coating and tested the hypothesis that surface heparinization limited to the oxygenator and the arterial filter will ameliorate systemic inflammation and preserve platelets during cardiopulmonary bypass (CPB). METHODS: In a prospective double-blind study, 159 patients underwent coronary revascularization using closed-system CPB with systemic heparinization, mild hypothermia (33 degrees C), a hollow-fiber oxygenator, and an arterial filter. The patients were randomly divided in three groups. In group A (controls, n = 51), surface heparinization was not used. In group B (n = 52), the extracorporeal circuits were totally surface-heparinized with Bioline coating. In group C (n = 56), surface heparinization was limited to oxygenator and arterial filter. RESULTS: No significant difference was noted in patient characteristics and operative data between groups. Operative (30-day) mortality was zero. Platelet counts dropped by 12.3% of pre-CPB value among controls at 15 minutes of CPB, but were preserved in groups B and C throughout perfusion (p = 0.0127). Platelet factor 4, plasmin-antiplasmin levels, and tumor necrosis factor-alpha increased more in controls during CPB than in groups B or C (p = 0.0443, p = 0.0238 and p = 0.0154 respectively). Beta-thromboglobulin, fibrinopeptide-A, prothrombin fragments 1 + 2, factor XIIa levels, bleeding times, blood loss, and transfusion requirements were similar between groups. Intensive care unit stay was shorter in groups B and C than in controls (p = 0.037). CONCLUSIONS: Surface heparinization with Bioline coating preserves platelets, ameliorates the inflammatory response and is associated with a reduced fibrinolytic activity during CPB. Surface heparinization limited to the oxygenator and the arterial filter had similar results as totally surface-heparinized circuits.     

Extracorporeal carbon dioxide removal performed with surface-heparinized equipment in patients with ARDS

To avoid the drawbacks of systemic anticoagulation during prolonged extracorporeal circulation in patients with adult respiratory distress syndrome (ARDS) a heparinization technique has been developed by which partially degraded heparin can be covalently end-point attached to the surface of the equipment constituting the extracorporeal circuit (Carmeda Bio-Active Surface, CBAS) thereby localizing the anticoagulatory effect. Since 1986 we have used extracorporeal circuits and membrane lungs coated with the CBAS for extracorporeal lung assistance (ECLA) in 14 patients suffering from ARDS. The patients were on ECLA for 3 to 55 days with a survival rate of 43%. Our experience so far is that by using equipment coated with CBAS it is possible to perform long-term extracorporeal circulation with a minimum of intravenously administered heparin, thus avoiding the risk of major coagulation defects.     

HEPARIN-REBOUND IN THE EARLY POSTOPERATIVE PHASE FOLLOWING CARDIOPULMONARY BYPASS

The incidence of the ‘heparin-rebound’ phenomenon after protamine neutralization of systemic heparinization required for cardiopulmonary bypass (CPB) was investigated. Heparin-effect was detected in 43% of patients studied at 2h, 31% at 4h, and 37% at 8h after reversal of circuit heparin on CPB. Heparin-rebound was shown to be associated with a small but significant increase in postoperative bleeding which was not of clinical importance.     

Heparin-coated versus uncoated extracorporeal circuit in patients undergoing coronary artery bypass graft surgery

OBJECTIVE: To assess the effect of heparin-coated circuits on bleeding, transfusion, and platelet count in patients undergoing primary coronary artery bypass grafting with full heparinization. DESIGN: Randomized, double-blind study. SETTING: Tertiary-care academic medical center. PARTICIPANTS: Eighty-eight patients undergoing coronary artery bypass grafting requiring cardiopulmonary bypass (CPB) without previous sternotomy. INTERVENTIONS: Subjects received either a heparin-coated or an uncoated extracorporeal circuit for CPB. Heparin, 300 micro/kg, was administered, and supplemental amounts were administered to maintain an activated coagulation time of greater than 480 seconds. Platelet counts were determined during CPB. Mediastinal chest tube drainage was collected in the intensive care unit for 24 hours. MEASUREMENTS AND MAIN RESULTS: The mean platelet counts were similar between the groups during CPB. There was no significant difference in 24-hour mediastinal chest tube drainage (mean +/- standard deviation; median) between the heparin-coated (n = 44, 1096 +/- 401, 1015 mL) and uncoated group (n = 44, 1150 +/- 548, 1040 mL; p = 0.91). The heparin-coated group received less allogeneic packed red blood cells (0.9 +/- 1.6, 0.0 v 1.5 +/- 1.8, 1.0 U; p = 0.04). CONCLUSIONS: The use of a heparin-coated or uncoated cardiopulmonary bypass circuit and full heparinization marginally reduced only red blood cell transfusion but was not associated with platelet sparing or reduced perioperative bleeding.     

The impact of heparin-coated cardiopulmonary bypass circuits on pulmonary function and the release of inflammatory mediators

Reduction of the inflammatory reaction with the use of heparin coating has been found during and after cardiopulmonary bypass (CPB). The question remains whether this reduced reaction also decreases the magnitude of CPB-induced pulmonary dysfunction. We therefore evaluated the effects of a heparin-coated circuit versus a similar uncoated circuit on pulmonary indices as well as on inflammatory markers of complement activation (C3b/c), elastase-alpha(1)-antitrypsin complex, and secretory phospholipase A(2) (sPLA(2)) during and after CPB. Fifty-one patients were randomly assigned into two groups undergoing coronary artery bypass grafting with either a heparin-coated (Group 1) or an uncoated (Group 2) circuit. During CPB, a continuous positive airway pressure of 5 cm H(2)O and a fraction of inspired oxygen (FIO(2)) of 0.21 were maintained. Differences in favor of the coated circuit were found in pulmonary shunt fraction (P < 0.05), pulmonary vascular resistance index (P < 0.05), and PaO(2)/FIO(2) ratio (P < 0.05) after CPB and in the intensive care unit. During and after CPB, the coated group demonstrated lower levels of sPLA(2). After CPB, C3b/c and the elastase-alpha(1)-antitrypsin complex were significantly less in the coated group (P < 0.001). The coated circuit was associated with a reduced inflammatory response, decreased pulmonary vascular resistance index and pulmonary shunt fraction, and increased PaO(2)/FIO(2) ratio, suggesting that the coated circuit may have beneficial effects on pulmonary function. The correlation with sPLA(2), leukocyte activation, and postoperative leukocyte count suggests reduced activation of pulmonary capillary endothelial cells. IMPLICATIONS: Heparin coating of the extracorporeal circuit reduces the inflammatory response during cardiopulmonary bypass. Analysis of indices of pulmonary function indicates that use of heparin coating may result in less impaired gas exchange.     

Hypothermia with heparin-coated circuits and low dose systemic heparinization in neurosurgery

The purpose of this study was to evaluate the safety of profound hypothermic circulatory arrest with heparin-coated circuits and low dose systemic heparinization in the treatment of cerebral aneurysms. Surgery for giant intracranial aneurysms not operable using standard neurosurgical techniques was performed in 8 patients. All patients were placed on cardiopulmonary bypass using the closed-chest technique, except for the first patient who underwent open-chest bypass. Heparin was administered systemically (3,000 IU) and into the circuit (1,500 IU). Total circulatory arrest was begun at 20 degrees C. The D-dimer, alpha2 plasmin inhibitor-plasmin complex, thrombin-antithrombin III, and beta-thromboglobulin concentrations were measured to evaluate the changes in the coagulation and fibrinolytic systems during bypass. There were no neurologic or cardiac complications. None of the indicators of platelet activation, coagulation, or fibrinolysis were elevated. Hypothermic circulatory arrest combined with heparin-coated circuits and low dose systemic heparinization is safe for use in neurosurgery.     

Biocompatibility of Heparin-Coated Membrane Oxygenator During Cardiopulmonary Bypass

Abstract: The biocompatibility of the cardiopulmonary bypass (CPB) circuit, in which an oxygenator is solely heparinized, was assessed by systemic inflammatory reactions as an indicator during CPB. Fourteen patients, 11 males and 3 females, underwent coronary artery bypass surgery and were randomly divided into 2 groups of 7 patients each. For the heparin–coated oxygenator group (Group H), a heparin–coated membrane oxygenator was used in the CPB circuit, and in the control (Group C) an uncoated membrane oxygenator was employed. Systemic inflammatory reactions, such as platelet activation, prostaglandin production, complement activation, and activated granulocyte released substance, were measured prior to, during, and 6 h after CPB. The number of platelets decreased after protamine administration in both groups (14. 5 ±4. 7 times 10⁴/μl in Group H and 13. 8 ± 8. 7 times 10⁴/μd in Group C) and returned to baseline levels in Group H while it remained decreased in Group C at 6 h after CPB. The platelet factor 4 level was significantly lower in Group H (181 ± 40 ng/ml) than in Group C (297 ±131 ng/ml) after protamine administration. Thromboxane–B₂ (TXB₂) rose during CPB in both groups; however, there were significantly different levels of TXB₂ between the 2 groups at 60 min after CPB (293±258 pg/ml in Group H versus 408 ± 120 pg/ml in Group C) and after protamine administration (259 ± 122 pg/ml in Group H versus 709 ± 418 pg/ml in Group C). Plasma concentrations of granulocyte elastase were significantly lower in Group H at 30, 60 and 90 min, immediately after, and post–CPB than those of Group C. Although the oxygenator was solely heparinized in the CPB circuit, it was sufficiently effective to reduce inflammatory reactions during coronary artery bypass operation, and the heparin–coated surface seems to be more endothelium–like.     

Duroflo II heparin bonding does not attenuate cytokine release or improve pulmonary function

BACKGROUND: Comparison of the cytokine generation and leukocyte activation properties of Duroflo II heparin bonded bypass circuit (Baxter Healthcare Corp, Compton, UK) and the conventional cardiopulmonary bypass circuit. Attempt to correlate these to pulmonary dysfunction postoperatively. METHODS: Forty patients undergoing elective, isolated coronary artery bypass grafting were randomly allocated to have either plain extracorporeal circuits (group C) or heparin bonded extracorporeal circuits (group H). Full systemic heparinization was used in all patients. The inflammatory response was assessed by measuring plasma levels of interleukin-6, interleukin-8, interleukin-10, and polymorphonuclear elastase. Gas exchange was assessed by measuring the PaO2/FIO2 ratio. RESULTS: Significant impairment of oxygenation was seen in both groups with the lowest values at the end of the operation before a gradual return to normal during the next 6 hours. There were no differences between the groups in gas exchange or times to extubation. There were significant elevations in all the cytokines, with interleukin-6 levels peaking at 4 hours in group H and 24 hours in group C, before starting to return to normal at 48 hours. The patterns of interleukin-8 and interleukin-10 rise were identical in the two groups. Polymorphonuclear elastase reached a peak at the end of the operation in group H and remained elevated up to 24 hours, whereas levels continued to rise in group C up to 4 hours. There were no significant differences in levels between groups at any time. There were no differences between the groups in blood loss or blood product usage. CONCLUSIONS: Cardiopulmonary bypass induces a systemic inflammatory response with release of cytokines and activation of leukocytes. This correlates with the severe deterioration in pulmonary gas exchange from preoperative levels up to 6 hours postoperatively (p < 0.05). In the presence of systemic heparinization, Duroflo II heparin bondingtf the circuits has minor effects on the pattern of evolution of this inflammatory response.     

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.     

Neutrophil lysosomal enzyme release and complement activation during cardiopulmonary bypass

Complement activation and neutrophil degranulation were concomitantly studied during uncomplicated cardiopulmonary bypass (CPB). Plasma concentrations of complement factor C4, complement split product C3d, the neutrophil lysosomal enzyme elastase complexed with alpha 1-proteinase inhibitor (PI) and fibronectin were measured in 12 patients, C3d and elastase/PI increased significantly during CPB (volume-corrected results). The C3d rise was almost linear, whereas elastase/PI showed exponential increase. Mean elastase/PI and mean C3d concentrations at different times during CPB covaried closely. The study showed that during CPB neutrophil lysosomal enzyme release is intimately related to complement activation, although activation of the two systems may be caused by a common third activator within the extracorporeal circuit.     

Heparin–coated circuit during cardiopulmonary bypass

A prospective randomized study was performed to investigate the effect of surface coating with covalently endpoint–attached heparin (Carmeda Bio Active Surface) and reduced general heparinization on haematological indices and complement C5 activation. Care was taken to optimize the rheological design of the system using centrifugal pump and a closed system without venting or machine suction. Twenty patients scheduled for aortocoronary bypass grafting (EF > 0.5) participated in the study. Ten patients were randomized to be treated with heparin–coated equipment (CBAS) and reduced i.v. heparin (1.5 mg kg^-1) while 10 patients treated with identical but noncoated equipment and full heparinization (3 mg–kg^-1) served in a Control group. A vacuum suction was used to collect the blood from the operating field and it was autotransfused at weaning from extracorporeal circulation (ECC). Blood samples were obtained from the venous (precircuit) and arterial (postcircuit) side. We used a new and very specific method for detection of C5a based on monoclonal antibodies. The concentration of C5a was low in both groups during the operation but a significant increase was seen on days 1 and 2. In the Control group there was an increase from 10.2 ngml^-1±1.2 to 27.5 ng ml^-1 ± 4.8 on day 2 and in the CBAS group from 10.7 ng ml^-1 ± 1.2 to 35.6 ng ml^-1 ± 11.6 on day 2 (NS between groups). The granulocytes and total leukocyte count increased at the end of ECC and was maintained at the elevated level throughout the study period. The amount of free haemoglobin was high in the autotransfused blood in both groups. The present results confirm the feasibility of reducing general heparin when using heparin–coated systems but the study does not support the superiority of such coating with regard to biocompatibility in short procedures with a Theologically optimized circuit. The potential benefit from reduced heparin and protamine has not been fully evaluated.     

Comparative Study of the Effect on Clinical Outcome of the Use of an Open Circuit and the Use of a Closed Circuit in Cardiopulmonary Bypass for a Graft Replacement of the Descending Thoracic or Thoracoabdominal Aorta

Purpose. We studied the benefits of reduced systemic heparinization in a heparin-coated cardiopulmonary bypass (CPB) system for graft replacement of the descending thoracic (TA) or thoracoabdominal aorta (TAA). Methods. Fifty-five patients were assigned to two groups: one group in which closed CPB circuits with reduced heparinization by elimination of the hard shell reservoir were used (group A, n = 36) and one group in which open circuits with full heparinization were used (group B, n = 19). Results. The transfusion requirement tended to be greater as the duration of CPB increased, even in group A. The incidences of renal dysfunction in two groups were not significantly different. Only the incidence of pulmonary dysfunction was significantly higher in group B. A reduction of systemic heparinization had no benefit for perioperative bleeding. In the TAA operation, the total amount of hemorrhaging in group A was greater than that in group B, but the difference was not significant. Conclusions. No beneficial effects of the use of heparin-coated CPB circuits on the amount of perioperative bleeding and postoperative organ damage, including renal dysfunction, were found in this study. However, our findings suggest that it may be better to avoid the use of closed CPB circuits in operations with a prolonged duration of CPB, such as a TAA operation.     

Low dose systemic heparinization combined with heparin-coated extracorporeal circulation. Effects related to platelets

BACKGROUND: A heparin coated cardiopulmonary bypass system combined with full and low dose systemic heparinization in coronary bypass surgery was investigated in a prospective, randomised study. Roller pumps, coronary suction and an open cardiotomy reservoir were used. METHODS: One hundred and nineteen patients were divided into 3 groups: group A (n=39) had a standard uncoated extracorporeal circulation (ECC)-set and systemic heparin was given in an initial dose of 400 IE/kg body weight. During ECC activated clotting time (ACT) was kept at = or >480 sec. Group B (n=42) had the same ECC-set completely coated with low molecular weight heparin, i.v. heparin was administered in the same dose as in group A, ACT was again kept at = or >480 sec. Group C (n=38) had the same coated ECC set as group B, but i.v. heparin was reduced to 150 IE/kg and during ECC ACT was maintained of = or >240 sec. RESULTS: Platelet decrease was significantly less in both groups utilizing coated circuitry as compared to control group A. Activation of thrombocytes as marked by b-thromboglobulin (not PF4) was significantly decreased in patients treated with coated circuits combined with low dose systemic heparinization and postoperative bleeding was significantly reduced. CONCLUSIONS: We conclude that in heparin coated extracorporeal circulation combined with either full dose or reduced systemic heparinization compared to uncoated circuits platelet count reduction is significantly less. Platelet activation as marked by b-thromboglobulin and postoperative blood loss are decreased with coated equipment and low i.v. heparinization.     

Complement conversion and leukocyte kinetics in open heart surgery

Complement conversions and a pulmonary leukocyte sequestration were observed during cardiopulmonary bypass (CPB) in all of twenty patients who received open heart surgery. A systemic neutropenia was initially observed in the early phase of CPB, and it subsequently turned into a systemic neutrocytosis during the late phase of it. A significant leukocyte sequestration was found in the pulmonary circulation during CPB coincidently with the systemic neutropenia. The contribution of the transpulmonary sequestration to the leukopenia was major, being as high as 80 per cent. Plasma C3, C4, and CH50 levels rapidly decreased following the commencement of CPB. Alterations of the C3 molecule in the patients’ plasma were demonstrated using the immunoblotting method. The appearances of C3a and C3b with the apparent molecular weights of 10,000 and 170,000 respectively, might be evidence of the complement activation during CPB. Another type of alteration in the C3 molecule was observed in the generation of a new fragment with the apparent molecular weight of 14,000. The appearance of this fragment, which did not share common epitopes with C3a, might suggest the consumption of complement components during CPB, unrelated to the activation of the complement systems.     

No benefit of reduced heparinization in thoracic aortic operation with heparin-coated bypass circuits

BACKGROUND: Heparin coating of the cardiopulmonary bypass circuit attenuates inflammatory response and confer clinical benefits in cardiac operations. The positive effects may be amplified with reduced systemic heparin dosage. We studied markers of inflammation and coagulation in thoracic aortic operations with heparin-coated circuits and standard vs reduced systemic heparinization. METHODS: Thirty patients were randomized to standard (group S; 300 IU/kg initially; activated clotting times [ACT] > 480 seconds; 5,000 IU in prime; n = 16) or reduced (group R; 100 IU/kg initially; ACT > 250 seconds; 2,500 IU in prime; n = 14) dose systemic heparin. The following markers were analyzed perioperatively: (a) inflammatory response; acute phase cytokine interleukin-6, and granulocytic proteins myeloperoxidase and lactoferrin; (b) complement activation; factor C3a and the C5a-9 terminal complement complex [TCC]; and (c) coagulation; thrombin-antithrombin III complex. RESULTS: The clinical outcome did not differ between groups. Four (29%) patients in group R had a perioperative thromboembolic event. All studied markers were significantly elevated during and throughout cardiopulmonary bypass in both groups. Maximal values were higher in group R for all variables except for TCC. There were no statistically significant intergroup differences regarding markers of inflammation, complement activation, or coagulation activation. CONCLUSIONS: The blood trauma in thoracic aortic operation is extensive, as reflected by the elevation of the studied biochemical markers, even when heparin-coated cardiopulmonary bypass circuits are used. In this study, we did not detect any benefits, either biochemical or clinical, of reducing the dose of systemic heparin.     

Experimental research with synthetic copolymer-coated cardiopulmonary bypass circuits: inflammatory and thrombogenicity analysis

This study aimed to assess complement system activation and index of thrombogenicity and platelet aggregation between synthetic copolymer-coated cardiopulmonary bypass (CPB) circuit and conventional CPB circuit. Twenty-six pigs were equally divided into two groups--the conventional group and the coated group. They were placed on CPB for 90 min, and blood samples were collected at three different time points (T0, right before CPB establishment; T1, 45 min after starting CPB; and T2, 90 min after starting CPB) to measure total count of inflammatory cells (leukocytes, neutrophils, lymphocytes, and platelets) and serum levels of fraction C3 of complement system. Upon completion of the 90-min CPB, fragments of different compartments of the CPB circuit were taken for assessing index of thrombogenicity and platelet aggregation. There were no differences between both groups regarding total count of leukocytes, neutrophils, and lymphocytes; however, there was a lower count of platelets at T2 in the coated group (P = 0.020). The serum level of fraction C3 was lower in the coated group at T1 (P = 0.020) and T2 (P = 0.017). Higher index of thrombogenicity and platelet aggregation were detected in the conventional group (77% of the animals within the conventional group) than in the coated group (46% of the animals within the coated group). In conclusion, in heart surgery requiring CPB, the use of synthetic copolymer-coated CPB circuit may be useful to reduce complement system activation, as well as attenuating index of thrombogenicity and platelet aggregation.