Influence of Two Blood Conservation Techniques (Cardiotomy Reservoir Versus Cell-Saver) on Biocompatibility of the Heparin Coated Cardiopulmonary Bypass Circuit During Coronary Revascularization Surgery

A bstract Blood conservation during cardiac surgery is critically important because of the inherent risks in homologous blood transfusions. Two techniques for the intraoperative conservation of blood—retransfusion of the red cells using a cell-saver (CS), or retransfusion of the blood using a cardiotomy suction (CTR) system—were compared using biocompatibility markers, granulocyte activation, and production of oxygen-free radicals (OFR). In the CTR group, heparin coated circuits with an uncoated cardiotomy reservoir were used. For the CS group, identical heparin coated cardiopulmonary bypass (CPB) sets, without a cardiotomy reservoir but with a CS, were used. In each group, eight patients had coronary artery bypass grafting performed. The capacity of the whole blood and the granulocytes to produce OFR was estimated by a chemiluminescence, and granulocyte activation was measured as release of the granulocyte granule proteins myeloperoxidase (MPO) and lactoferrin. A significantly reduced capacity to produce OFR by the whole blood was noted at 45 minutes of CPB in the CTR group (68%± 17% vs 94%± 16% in the CS group). MPO release was higher after 3 hours (p = 0.05) and 20 hours (p < 0.05), postoperatively, in the CTR group (417 ± 77 μg/L and 257 ± 31 μg/L vs 246 ± 25 μg/L and 164 ± 12 ng/L, respectively, in the CS group). We conclude that the heparin coated CPB circuit with the uncoated cardiotomy reservoir may be less biocompatible than the identical CPB set used together with the CS.     

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.     

Efficacy of a new coating material, PMEA, for cardiopulmonary bypass circuits in a porcine model

BACKGROUND: A new coating material, poly-2-methoxyethyl acrylate (PMEA), was developed to improve the biocompatibility of cardiopulmonary bypass (CPB) circuits. METHODS: To investigate the efficacy of the PMEA coating for CPB circuits, we compared PMEA-coated circuits (group P, n = 6) with uncoated circuits (group C, n = 6) and heparin (covalent-bonded heparin, Hepaface)-coated circuits (group H, n = 6) in a porcine CPB model. RESULTS: Platelet counts were significantly preserved in groups P and H compared with those in group C (P versus C, p < 0.05). The plasma levels of thrombin-antithrombin complex and bradykinin were significantly lower at 120 minutes in groups P and H than in group C (thrombin-antithrombin: P versus C, p < 0.05; bradykinin: P versus C, p < 0.05). The amount of fibrinogen adsorbed onto the hollow fibers was markedly less in group P than in groups C and H. CONCLUSIONS: The PMEA coating was equal to heparin coating in preventing reactions induced by CPB circuits, and might be superior to heparin coating in suppressing the adsorption of plasma proteins such as fibrinogen. Thus, PMEA coating may be a suitable means for improving the biocompatibility of CPB circuits.     

Effects of Heparin Coating of Cardiopulmonary Bypass Circuits on In Vitro Oxygen Free Radical Production During Coronary Bypass Surgery

Abstract During cardiopulmonary bypass (CPB) oxygen free radicals (OFR) are formed, which can mediate reactions damaging tissue components. Blood contact with artificial surfaces during CPB leads to an activation of leukocytes, which are one of the sources of the OFR. Heparin coating of the CPB circuit reduces granulocyte activation. In the present study, the heparin-coated circuits with noncoated cardiotomy reservoirs (Group HC) were compared with noncoated, otherwise similar CPB sets (Group C). In each group, 8 patients were operated on for coronary revascularization. The release of granulocyte granule proteins myeloperoxidase (MPO) and lac-toferrin (LF) was evaluated. Production of OFR in the whole blood and in the granulocyte suspension were measured by chemiluminescence (CL). In both groups the whole blood CL declined during CPB. The whole blood CL induced by serum-opsonized zymosan, when enhanced by luminol, was significantly lower in Group HC at 45 min after CPB start (68 ± 6% of initial values in Group HC vs. 87 ± 6% in Group C, mean ± SEM) and 30 min after protaminization (54 ± 6% of initial values in Group HC vs. 72 ± 6% in Group C, mean ± SEM), and CL was significantly higher in Group HC at CPB end (83 ± 5% of initial values in Group HC vs. 67 ± 5% in Group C, mean ± SEM) when enhanced by lucigenin. CL of isolated granulocytes showed no significant differences between the groups. Release of MPO at CPB end and of LF 45 min after start of CPB and at CPB end were significantly lower in the heparin-coated CPB circuits.     

Correlation of ACT as measured with three commercially available devices with circulating heparin level during cardiac surgery

Automated activated clotting time (ACT) is utilized as the primary means of assessing anticoagulation status for cardiopulmonary bypass (CPB) procedures. Influences on the clotting cascade during CPB such as hypothermia, hemodilution, and platelet dysfunction are known to affect ACT. The recently introduced Thrombolytic Assessment System (TAS) has been reported to be less sensitive to changes in hemodilution and hypothermia during CPB than more conventional ACT devices. This study evaluated the ability of TAS, and two other commercially available automated ACT systems, the HemoTec and Hemochron, to correlate with circulating heparin levels. Reference standards for circulating heparin were determined by inactivation of factor Xa assay. Nineteen patients undergoing moderate hypothermic CPB served as subjects for this investigation. Blood samples were obtained for study at four time periods: 1) baseline (control), 2) post heparin administration (300-400 U/kg) prior to CPB, 3) during CPB, and 4) post protamine. Study results demonstrated a high correlation between the HemoTec and Hemochron (r = 0.99), increased heparin dose response on CPB compared to pre-CPB activity (p < 0.05), and a significant (p < 0.05) negative correlation between devices and patient hematocrit during CPB. Additionally, device correlation with anti-Xa assay during collection periods 2 and 3 showed negative correlations in each of the three devices evaluated. We conclude that all automated devices tested demonstrated an inability to predict circulating heparin at levels necessary for CPB, and that these discrepancies become magnified during CPB procedures.     

Hyaluronan based heparin free coated open and closed extracorporeal circuits for high risk coronary revascularization

This prospective randomized study compares the inflammatory response and fibrinolytic activation of fully coated/uncoated and open/closed extracorporeal circuits (ECC) in high risk patients. Over a 2-month period, 48 patients with EuroSCOREs 6 or greater undergoing coronary revascularization were prospectively randomized to one of the four perfusion protocols: Group 1: Closed and totally hyaluronan based heparin free coated (Vision HFO-GBS-HF, Gish Biomedical, Rancho Santa Margarita, CA) ECC with a soft-shell coated venous reservoir (SVR11S2-HFC, Gish Biomedical) and a hard-shell cardiotomy (CAPVRF44, Gish Biomedical) (n = 12); Group 2: Closed and totally uncoated identical ECC with soft-shell uncoated venous reservoir and a hard-shell cardiotomy (n = 12); Group 3: Open, totally hyaluronan based heparin free coated ECC (n = 12); and Group 4: Control-open, uncoated ECC (n = 12). Blood samples were collected at T1: Baseline; T2: 15 minutes after cardiopulmonary bypass (CPB) initiation; T3: before cessation of CPB; T4: 15 minutes after protamine reversal, and T5: in the intensive care unit. Serum IL-6 levels were significantly lower at T2 in all study groups, at T3 for coated groups, and T4 for closed+coated group (p < .05 versus control). Creatine kinase M-band (MB) levels in coronary sinus blood demonstrated well preserved myocardium after CPB in both coated groups versus Control (p < .05). Neutrophil CD11b/CD18 levels were significantly lower for all study groups versus control at T2, for both coated groups at T3 and only for closed + coated group at T4 (p < .05). Postoperative hemorrhage (mL) was 510 +/- 40 in closed + coated and 536 +/- 40 in open + coated groups (control: 784 +/- 48, p < .05). No significant differences in thrombin-antithrombin complex and free plasma hemoglobin were observed. Desorbed protein amount on ECC (mg/dL) was 1.7 +/- .01 in closed+coated, 2.01 +/- .01 in open+coated, and 3.3 +/- .015 in control groups (p < or = .05). Use of a closed and completely heparin free coated ECC may reduce neutrophil degradation, cytokine release characterized by improved clinical outcomes including reduced blood loss, reduced requirement for inotropes, and reduced atrial fibrillation.     

Comparison of heparin administration using the Rapidpoint Coag and Hepcon HMS

A retrospective chart review was conducted of patients who underwent cardiopulmonary bypass (CPB) to compare the quantities of heparin administered, postoperative blood loss, and homologous blood products transfused during their procedure and subsequent stay in the intensive care unit. The primary purpose of this review was to determine if any difference in heparin administration resulted when two different devices were used for dosing and monitoring heparin. Postoperative blood loss and amount of blood products transfused were also quantified, as any differences would potentially be a result of a difference in administration of heparin. The first group (n = 341) underwent CPB using the Hepcon HMS, Medtronic Inc., Minneapolis, MN, for heparin dosing and monitoring. The Rapid Point Coag, Bayer Healthcare LLC, Tarrytown, NY was used for the second group (n = 345). The two populations were compared for similarity on: age, body surface area (BSA), CPB time (minutes), aortic-cross clamp time (minutes), baseline activated clotting time, and baseline hematocrit. No significant difference was found between the two groups. The second group, using the Rapidpoint Coag, received less heparin during CPB than the group using the Hepcon HMS. In addition, there were decreases in amounts of some blood products transfused as well as mediastinal drainage from the Hepcon HMS to the Rapidpoint Coag group. A summary of the findings can be found in Table 1. A secondary purpose of this study was to determine the influence of hemodilution on the Heparin Management Test (HMT). Citrated whole blood was diluted to varying degrees at various concentrations to determine whether hemodilution with crystalloid would alter the HMT measurements. At all heparin levels and degrees of dilution, the HMT remained stable, with coefficients of variation (CV) of less than 5% at all heparin levels even while incorporating excessive crystalloid dilution (up to 75%).     

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.     

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.     

Matrix metalloproteinase inhibitor: differential effects on pulmonary neutrophil and monocyte sequestration following cardiopulmonary bypass

Acute respiratory distress syndrome (ARDS) following cardiopulmonary bypass (CPB), also known as "post-pump" or "post-perfusion syndrome" (PPS), results from sequential priming and activation of neutrophils. We hypothesized that chemically modified tetracycline (CMT-3) an inhibitor of neutrophil matrix metalloproteinase (MMP) and elastase, would prevent PPS. We performed histometric analysis of lung tissue from our porcine PPS model to correlate cellular sequestration and histologic injury with CMT-3 treatment. METHODS: Yorkshire pigs were randomized into five groups: Control (n = 3); CPB (n = 5); femoral-femoral bypass 1 hour; LPS (n = 7), Escherichia coli lipopolysaccharide (1 microgram/kg); CPB + LPS (n = 6); and CPB + LPS + CMT (n = 5), sequential insults and CMT-3. Protocol histometric analysis defined cellular and tissue components of lung injury. RESULTS: CMT-3 decreased neutrophil sequestration in the CPB + LPS + CMT-3 group (p < 0.0001 vs. CPB + LPS). There were no differences in monocytes between CPB + LPS and CPB + LPS + CMT treatment groups. CONCLUSIONS: CMT-3 attenuates neutrophil sequestration but has no effect on mononuclear sequestration in our PPS model. This finding supports current research on leukocyte chemokines and has important implications regarding mechanisms of CMT-3. Despite lack of monocyte response to CMT-3, PPS was prevented by inhibiting neutrophils alone; confirming the primary role of neutrophils in PPS.     

Biocompatibility of extracorporeal circulation. In vitro comparison of heparin-coated and uncoated oxygenator circuits

Oxygenator/tubing sets coated with endpoint-attached heparin were compared to uncoated sets in a dynamic model of extracorporeal circulation. Biocompatibility was assessed by evaluations of complement activation and platelet loss. The median concentration of C3 activation products increased gradually from 12 AU/ml at baseline to 65 AU/ml after 120 minutes in the uncoated sets and from 12 AU/ml to 19 AU/ml after 120 minutes in the coated sets (p less than 0.002). The median concentration of the terminal complement complex in the uncoated sets increased gradually from 3.1 AU/ml at baseline to 18.2 AU/ml after 120 minutes. In the coated sets the terminal complement complex reached a peak of 12.0 AU/ml at 15 minutes and returned to baseline values at 60 minutes. Median platelet loss at 120 minutes was 166 x 10(9) in the uncoated and 21 x 10(9) in the coated sets (p less than 0.01). Heparin coating thus improved biocompatibility by reducing both complement activation and platelet loss.     

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.     

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.     

A prospective, randomized study of cardiopulmonary bypass temperature and blood transfusion

BACKGROUND: We hypothesized that normothermic cardiopulmonary bypass (CPB) would be associated with decreased blood loss and allogeneic transfusion requirements relative to hypothermic CPB. METHODS: After obtaining institutional review board approval and informed patient consent, we conducted a prospective, randomized study of 79 patients undergoing CPB for a primary cardiac operation at normothermic (37 degrees C) (n = 44) or hypothermic temperature (25 degrees C) (n = 35). Blood loss and transfusion requirements in the operating room and for the first 24 hours in the intensive care unit were determined. A paired t test and rank sum tests were used. A p value of less than 0.05 was considered significant. RESULTS: The normothermic and hypothermic CPB groups did not differ in demographic variables, CPB or cross-clamp duration, heparin sodium or protamine sulfate dose, prothrombin time, or thromboelastogram results. There were no differences between the two CPB groups in blood loss or transfusion requirements. CONCLUSIONS: We found that when there was no difference in duration of CPB, normothermic and hypothermic CPB groups demonstrated similar blood loss and transfusion requirements even though other studies have shown hypothermia induces platelet dysfunction and alters the activity of the coagulation cascade.     

1，6—二磷酸果糖对体外循环期间中性粒细胞的影响

目的　研究体外循环下 1,6 二磷酸果糖 (FDP)对中性粒细胞 (PMNs)活化、释放的影响。方法　 2 0例先心病矫正术患者随机分成使用FDP( 2 2 0mg/kg)的观察组 (n =10 )和对照组 (n =10 ) ,动态观察中性粒细胞化学发光 (PMN CL)值、中性粒细胞内髓过氧化物酶 (MPO)及弹性蛋白酶(ELA)活性。结果　 ( 1)与阻断主动脉时对比 ,两组各时点PMN CL值均明显升高 (P <0 0 5、P <0 0 1或P <0 0 0 1) ,PMN MPO及ELA活性降低 (P <0 0 5或P <0 0 1) ,化学发光最高值、MPO及ELA活性最低值出现在主动脉开放后 (再灌注 ) 4 5分钟。 ( 2 )与对照组相比 ,在主动脉阻断 3 0分钟、主动脉开放后 (再灌注 ) 4 5分钟及 90分钟 ,观察组PMN CL值降低 ,PMN MPO及ELA活性升高 (P<0 0 5或P <0 0 1)。结论　 ( 1)体外循环时PMNs活化并释放多种活性物质 ,且主要发生于主动脉开放后 (再灌注 )早期。 ( 2 )FDP抑制PMNs的活化 ,减轻了PMNs的释放反应。     

Heparin monitoring during cardiopulmonary bypass surgery using the one-step point-of-care whole blood anti-factor-Xa clotting assay heptest-POC-Hi

The activated clotting time (ACT) generally used for monitoring heparinization during cardiopulmonary bypass (CPB) surgery does not specifically measure heparin anticoagulant activities. This may result in heparin over- or under-dose and subsequent severe adverse events. A new point-of-care whole blood clotting assay (Heptest POC-Hi [HPOCH]) for quantifying heparin anticoagulant activity specifically was compared with ACT and anti-factor Xa (anti-Xa) heparin plasma levels (Coatest heparin) in 125 patients undergoing CPB surgery. The analytical reliability of the HPOCH and the influence of preanalytical variables on assay results were also examined. The ACT and HPOCH clotting times determined throughout the entire observation period correlated closely (n=683; r = 0.80; p < .0001). Similarly, there was a significant linear correlation between HPOCH and Coatest anti-Xa levels (n=352; r = 0.87; p < .0001). Pre- and post-CBP values of HPOCH, ACT, and anti-Xa plasma levels correlated closely with each other (correlation coefficients between r = 0.90 and r = 0.99; p < .0001). During CPB, there was no significant relationship between ACT and whole blood or plasma heparin levels determined by HPOCH (n=157; r = 0.19) and the chromogenic anti-Xa assay (n=157; r = 0.04), respectively. In contrast, HPOCH and anti-Xa plasma levels correlated strongly during CPB (n=157; r = 0.57; p < .0001). However, bias analysis showed that the HPOCH and Coatest heparin could not be used interchangeably. The HPOCH was well reproducible and not influenced by aprotinin, hemodilution, or other factors affecting ACT. The HPOCH seems to be a promising new tool for specific on-site measurement of heparin activities in whole blood during CPB.     

The effects of complement activation during cardiopulmonary bypass. Attenuation by hypothermia, heparin, and hemodilution.

Complement activation was examined prospectively in 100 cardiopulmonary bypass (CPB) patients. Plasma C3a desArg (C3a) increased (cannulation: 234 +/- 33 ng/mL; 20 minutes on CPB: 622 +/- 51; 2 hours after CPB: 1143 +/- 109, p less than 0.0001). C3a at 2 hours was higher in the 13 patients requiring mechanical ventilation for longer than 1 day (1023 +/- 274) than in the 67 without respiratory complication (568 +/- 45, p less than 0.004). Five more patients were studied for neutrophil activation to confirm that a biologic effect of complement activation occurs during CPB; in these five patients C3a increased to 317% of baseline after 10 minutes on CPB with a corresponding rise in neutrophil cell surface receptors for the complement opsonin C3b (as measured by indirect immunofluorescence) to 168% (p less than 0.05). Both increases were sustained at 30 minutes. Temperature, dilution, and heparin were studied as variables relevant to CPB. Exposure of normal neutrophils to C5a in vitro caused an increase in C3b receptors which was dependent on temperature (0 specific fluorescence at 0 C, 30 at 25 C, 180 at 30 C, and 275 at 37 C). Generation of C3a and C5a in normal serum by zymosan was also temperature-dependent (ng/mL C5a generated: 0.7 at 25 C, 200 at 30 C, and 897 at 37 C; ng/mL C3a generated: 546 at 25 C, 10,872 at 30 C, and 65,667 at 37 C). Serum dilution to 33% decreased ng/mL C5a generated in the same system from 200 to 76 with no effect on C3a. Addition of heparin to 20 U/mL decreased ng/mL C3a generated from 10,872 to 913 and C5a from 200 to 8. Thus, hypothermia, dilution, and heparin protect CPB patients from complement activation by reducing both generation of C3a/C5a and the subsequent cellular response of neutrophil activation.     

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.     

Clinical performance and biocompatibility of novel hyaluronan-based heparin-bonded extracorporeal circuits

We tested documented in vitro and ex vivo advantages of novel hyaluronan based heparin bonded extracorporeal circuits in a prospective randomized study. During the period from June until September 2005, 40 patients undergoing reoperation for coronary artery bypass grafting were allocated into two equal groups (n = 20): Group 1 was treated with hyaluronan-based heparin-bonded circuits and group 2 was treated with uncoated control circuits. Complete blood count, fibrinogen, albumin, C3a, interleukin-2 levels, and thromboelastographic data were documented after induction of anesthesia (T1) and heparin administration before cardiopulmonary bypass (CPB) (T2), 15 minutes after initiation of CPB (T3), before cessation of CPB (T4), 15 minutes after reversal with protamine (T5), and the first postoperative day at 8:00 a.m. (T6). Hollow fibers were collected for consecutive biomaterial analysis by optical and scanning electron microscopy (SEM). Desorbed protein deposition on fibers was compared by spectrophotometry. Leukocyte counts were lower in T4-T6 in group 1 (p < .05). Platelet counts demonstrated significant differences at T4 and T5 in coated group (p < .05). Albumin and fibrinogen levels were better preserved in Group 1 at T4, T5 and T4, T6, consecutively (p < .05). C3a and IL-2 levels were lower at T3-T5 and T4-T5 in intervention group (p < .05). Postoperative hemorrhage was 412 +/- 50 mL in group 1 and 684 +/- 50 ml in group 2 (p < .05). Respiratory support time was shorter in group 1 versus control (p < .05). Platelet adhesion was significantly lower in intervention group. Amount of desorbed protein was 1.44 +/- 0.01 mg/dL in group 1 and 1.94 +/- 0.01 mg/dL in control (p < .05). SEM and spectrophotometry demonstrated better surface preservation in the hyaluronan coated group. Novel hyaluronan-based heparin-bonded circuits reduce platelet adhesion-aggregation and protein adsorption and provide better perioperative clinical parameters through platelet, albumin, and fibrinogen-sparing effects.     

Performance characteristics of hemofilters with heparin surface coating: an experimental study

Heparin surface coated hemofilters and tubing sets were evaluated in comparison to identical but uncoated controls in 8 bovine experiments (74+/-6 kg). No heparin was given (neither systemically nor in the priming fluid). The hemofilters were primed with one liter of Ringer's lactate in both groups and the maximal filter performance (arterial line pressure 300 mmHg; transmembrane pressure (TMP) 500 mmHg) was measured over 6 hours or until filter occlusion. All coated and one control filter remained functional during the scheduled 6 hours. The mean filter patency was 360+/-0 minutes for coated versus 210+/-99 minutes for uncoated (p less than 0.01). Mean blood flow at 1 hour and 6 hours was 675+/-114 and 580+/-96 ml/min for coated versus 432+/-183 and 25+/-43 for uncoated (NS; p less than 0.01). Mean filter output during the 6th hour and total filter output over 6 hours was 4225+/-998 ml and 21779+/-4273 for coated versus 400+/-692 and 7717+/-9757 for uncoated (p less than 0.01; p<0.01). Mean lactatedehydrogenase (LDH) levels before and 30 minutes after hemofiltration were 1855+/-411 IU and 2007+/-635 for coated versus 2160+/-411 and 1945+/-500 for uncoated (NS; NS). The heparin coated hemofilters demonstrated improved thromboresistance resulting in superior filter performance. There was no evidence of increased blood trauma.