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.     

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.     

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.     

Comparative study of biocompatibility between the open circuit and closed circuit in cardiopulmonary bypass.

The theoretical benefit of a centrifugal pump or heparin coating demonstrated through in vitro or in vivo studies is not recognizable in cardiopulmonary bypass (CPB) during chemical open heart surgery. The objective of this study was to investigate the influence of the interface of air and blood in current CPB with an open circuit system and its relative significance in relationship to the heparin dose and heparin coating. Using the same oxygenator and circuit, an open circuit and closed circuit CPB with the same priming volume were prepared for a 4 h perfusion experiment using diluted and heparinized (3.6 U/ml) fresh human blood. In these experiments, both heparin-coated and noncoated circuits were examined. Blood was sampled before and 2, 30, 60, 120, and 240 min after the start of perfusion, and the platelet and white blood cell counts and beta-thromboglobulin (beta-TG) and C3a levels were measured. The amount of adsorbed protein in the hollow fibers was also measured after retrieval. Although the results demonstrated significantly better biocompatibility of the heparin-coated circuit than the noncoated circuit, the difference between the open and closed circuits was unexpectedly small and insignificant with either the heparin-coated circuit or noncoated circuit. In contrast, the C3a level was higher in the closed circuit than the open circuit. However, the amount of adsorbed protein was markedly lower in the closed circuit (0.7 microgram/cm2) than in the open circuit (11.1 micrograms/cm2). An immunoblot of the adsorbed protein showed a higher density of fibrinogen bands and conversion to fibrin in the open circuit. We speculate that the lower blood C3a level in the open circuit suggests that C3a was taken in by the adsorbed protein. In conclusion, analysis of the adsorbed protein indicates the lower biocompatibility of the open circuit. Similar experiments with less heparin use and more severe conditions will be necessary to elucidate the essential benefit of making a CPB closed circuit.     

Heparin-Coated Equipment Reduces Complement Activation during Cardiopulmonary Bypass in the Pig

Complement activation was studied during cardiopulmonary bypass (CPB) in the pig. One group of animals was perfused for 2 h using a standard extracorporeal circuit including a hollow fiber membrane oxygenator with full systemic heparinization. Another group was treated in the same way, except that bypass was performed through a heparin-coated CPB circuit (Carmeda Bio-Active Surface, CBAS) and systemic heparinization was reduced by 75%. It was found that complement activation during CPB, measured as changes in the ratio C3d/C3, was significantly less in the CBAS group, most probably reflecting a better biocompatibility.     

Heparin-Coated Cardiopulmonary Bypass Circuit: Clinical Effects in Pediatric Cardiac Surgery

OBJECTIVES: Heparin-coated cardiopulmonary bypass (CPB) circuits have been reported to reduce complement activation and the inflammatory response associated with CPB. We retrospectively compared patients utilizing heparin-coated perfusion circuits with those using noncoated circuits to determine the clinical effects of the different circuits in pediatric cardiac surgery. METHODS: Between July 1995 and July 1997, 203 patients weighing < 10 kg underwent cardiac surgery, 153 patients using heparin-coated bypass circuits and 50 patients using noncoated circuits. The 50 patients operated on with the noncoated circuit (Group N) were matched to 100 patients operated on with coated circuits (Group H) in age, weight, and type of procedure. Urine output during bypass, blood products used after bypass, postoperative ventilation days, hospital stay, morbidity, and mortality were compared between these groups. RESULTS: Body weight, perfusion time, and procedure time were not different between the two groups. Urine output during bypass was notably greater in Group H than in Group N (11.3 +/- 10.5 mL/kg per hour vs 4.8 +/- 3.1 mL/kg per hour, respectively, p < 0.0001). Postoperative mechanical ventilation markedly decreased in Group H (Group H vs N = 2.8 +/- 2.7 days vs 5.1 +/- 7.5 days, respectively, p < 0.05). Red blood cell usage, hospital stay, morbidity, and mortality were not statistically different, although there was a tendency toward decreased transfusion of red cell and platelets in Group H (Group H vs N = 61.2 +/- 121.1 mL/kg vs 102.0 +/- 176.7 mL/kg, respectively, in red cell, p = 0.15; and Group H vs N = 7.9 +/- 13.7 mL/kg vs 13.2 +/- 24.5 mL/kg, respectively, in platelets, p = 0.16). CONCLUSIONS: Patients operated on with the use of heparin-coated circuits had increased urine output during bypass and required less time postoperatively on the ventilator. These results suggest a reduction in the acute inflammatory response, capillary leakage, and overall systemic edema. We now routinely use coated circuits on all pediatric pump cases.     

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 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.     

Heparin-coated Cardiopulmonary Bypass Circuits Reduce Circulating Complement Factors and Interleukin-6 in Paediatric Heart Surgery

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits. Plasma levels of acute phase reactants, interleukins, granulocytic proteins and complement factors were measured. All were significantly elevated after CPB. Levels of complement factor C3a (851 (791-959) ng/ml [median with quartiles] in group C, 497 (476-573) ng/ml in group HC, p &lt; 0.001), Terminal Complement Complex (114 (71-130) AU/ml in group C, 35.5 (28.9-51.4) AU/ml in group HC, p &lt; 0.001), and interleukin-6 (570 (203-743) pg/ml in group C, 168 (111-206) pg/ml in group HC, p = 0.005), were significantly reduced in group HC. Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population, as reflected by significantly reduced levels of circulating complement factors and interleukin-6.     

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.     

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)     

Quantitative evaluation of heparin-coated versus non-heparin-coated bypass circuits during cardiopulmonary bypass

The extracorporealization of blood activates various elements of the fibrinolytic, coagulation, and complement systems. It is theorized that advancements in biocompatibility ameliorate many of the changes leading to improved patient management. The purpose of this study was to determine if heparin-coated circuit (HCC) utilization during cardiopulmonary bypass enhances patient outcomes in a cost-effective manner. A search of the English medical literature was completed to identify all clinical, prospective, randomized trials comparing HCC and non-HCC in patients undergoing coronary artery bypass grafting or valvular surgery. Twenty-six papers consisting of a sample size of 1515 patients were identified and included in the study parameters. The study distinguished between Duraflo II and Carmeda coating techniques and matched papers with different heparin loading doses, as well as use of a heparin-coated cardiotomy. Study parameters were matched for all papers and analyzed according to the availability of data. Statistically significant benefits of HCC were found in postoperative blood loss, time in the ICU, end bypass C3a, time to extubation, end bypass lactoferrin, and end platelet count, but not with respect to postoperative chest tube drainage, red blood cell transfusions, and end bypass TAT complex, D-dimers, and BTG. Data comparing the use of coated or uncoated cardiotomy utilization failed to demonstrate a benefit to heparin coating. Several immunological variables were ameliorated when Carmeda HCC was utilized, although data were insufficient to establish a cost-benefit analysis. In conclusion, heparin-coated circuitry provided statistically better results when compared to noncoated circuitry.     

Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in paediatric heart surgery

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits. Plasma levels of acute phase reactants, interleukins, granulocytic proteins and complement factors were measured. All were significantly elevated after CPB. Levels of complement factor C3a (851 (791-959)ng/ml [median with quartiles] in group C, 497 (476-573)ng/ml in group HC, p < 0.001), Terminal Complement Complex (114 (71-130) AU/ml in group C, 35.5 (28.9-51.4) AU/ml in group HC, p < 0.001), and interleukin-6 (570 (203-743) pg/ml in group C, 168 (111-206)pg/ml in group HC, p = 0.005), were significantly reduced in group HC. Heparin-coated CPB circuits improve the biocompatibility of CPB during heart surgery in the paediatric patient population, as reflected by significantly reduced levels of circulating complement factors and interleukin-6.     

Biocompatibility of poly2methoxyethylacrylate coating for cardiopulmonary bypass.

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

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.     

In vivo comparison study of FDA-approved surface-modifying additives and poly-2-methoxyethylacrylate circuit surfaces coatings during cardiopulmonary bypass

The purpose of this double-blind prospective and randomized study was to examine the effects of surface-modifying additives (SMAs) and poly-2-methoxyethylacrylate (PMEA) circuits on platelet count, platelet function (Sonoclot), postoperative chest tube drainage volume, peri- and postoperative blood product use, extubation time, and intensive care time. Terumo noncoated, Terumo-coated (PMEA), Cobe noncoated, and Cobe coated (SMA) circuits were evaluated to find the most cost-effective way to improve patient outcomes. We aimed to find if an additional charge for a coated CPB circuit would be recovered by reducing other patient costs (blood transfusions, intensive care unit time, and bring back postoperative bleeding). An initial literature review revealed the comparison of PMEA circuits vs. noncoated circuits and SMA circuits vs. noncoated circuits in both adult and porcine models. Both SMA- and PMEA-coated circuits decreased platelet consumption, platelet factor release, and the overall perioperative inflammatory response while on cardiopulmonary bypass (CPB). The question not answered in an initial search was simply, "which coated circuit is best for the patient: SMA or PMEA?" Research comparing the above coated circuits each other was not found. The study was approved by the Institutional Review Board. Thirty patients were scheduled for elective coronary artery bypass grafting and/ or valvular repair or replacement surgery. These 30 patients were randomized as 10 patients to Terumo X-Coating (PMEA surface coating) (CT), 10 patients to Cobe Smart-X coating (SMA surface coating; CC), 5 patients to Terumo noncoated tubing (NCT), and 5 patients to Cobe noncoated tubing (NCC). Informed consent was obtained from each patient before surgery. The data showed no statistically significant relationship between platelet counts, platelet function (Sonoclot), postoperative chest tube drainage volume, peri- and postoperative blood products, intensive care unit time, or total hospital length of stay. Analysis revealed statistically significant clinical associations of extubation time and protamine dose with treatment group. This study provided evidence that SMA- and PMEA-coated circuits do not improve platelet consumption or decrease blood product use for patients undergoing CPB. There was statistical significance with a reduction in extubation time and total protamine requirement needed to return activated clotting time (ACT) to baseline post-CPB. Although the use of SMA and/or PMEA circuits during CPB has clinical benefit to the CPB patient, an additional charge for the specialty circuit may not be realized.     

Heparin-coated circuits (Duraflo II) with reduced versus full anticoagulation during coronary artery bypass surgery

BACKGROUND: Introduction of completely heparin-coated cardiopulmonary bypass (CPB) circuits combined with reduced systemic anticoagulation has been shown to reduce postoperative bleeding and requirements for allogeneic transfusions after cardiac surgery. However, some uncertainty exists whether this effect is due to the reduced amount of heparin or to the heparinized surface itself. Therefore, a retrospective study was undertaken, comparing two different anticoagulation protocols applied to coronary artery bypass patients treated with identical heparin-coated CPB equipment. METHOD: Over a 12 month period all coronary artery bypass patients operated with extracorporeal circulation were subjected to a Duraflo II heparin-coated circuit (Baxter Healthcare Corp, Bentley Laboratories Division, Irvine, Calif) and full heparin dose (activated clotting time [ACT] > 480 seconds; Group F, n = 651). Over the next 24 months, all coronary patients who were treated with an identical circuit combined with reduced systemic heparinization (ACT > 250 seconds) were included in Group R (n = 675). Except for the different anticoagulation protocols, all treatment regimens before, during, and after the operation remained unchanged throughout the study period. RESULTS: There were no statistically significant differences in any major demographic or operative parameters. In Group R, the postoperative bleeding was mean 665 +/- 257 ml versus 757 +/- 367 ml in Group F (p < 0.0001), and the perioperative decrease in hemoglobin concentration was significantly lower in Group R (22 +/- 1.2 gm/L versus 25 +/- 1.3 gm/L, p < 0.0001). The time for postoperative ventilatory support was shorter in Group R (1.7 +/- 1.3 hours versus 1.9 +/- 1.1 hours in Group F, p = 0.0006), and the incidence of new episodes of atrial fibrillation after the operation was lower (26.4% in Group R versus 32.8% in Group F, p = 0.01). There were no significant differences in the incidences of perioperative myocardial infarction, stroke, transient neurological disturbances, physical rehabilitation, or mortality. No technical or coagulation problems were recorded in either group. CONCLUSION: The use of Duraflo II coated circuits for CPB combined with reduced anticoagulation decrease postoperative bleeding and hemoglobin loss compared with full heparin dose treatment. In addition, the intubation time was shorter and the incidence of postoperative atrial fibrillation was lower in the patients treated with low heparin doses.     

在体外及体外循环中抑肽酶对ACT的影响

选择健康献血员及心内直视手术病，观察抑肽酶对全血活化凝血时间的影响。结果：在体外肝素剂量与ＡＣＴ有显著线性相关。抑肽酶单狡应用并不使ＡＣＴ延，但与肝素合用可协同性延长ＡＣＴ值；在体外循环中抑肽酶延长ＡＣＴ的值更为显著，一般超过８００ｓ。结论：抑肽酶可与肝素协同性延长ＡＣＴ，体外循环中应用抑肽酶时应以ＡＣＴ大于８００ｓ作为肝素抗凝标准。     

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 Studies on Three Types of Heparin-Coated Cardiopulmonary Bypass Circuits

Abstract: In cardiovascular operations, we have usually used heparin-coated cardiopulmonary bypass circuits with low systemic heparinization. Three types of heparin-coated cardiopulmonary bypass circuits are available in Japan: 2 of the 3 have covalent heparin bonding, and the other has ionic heparin bonding. We studied these circuits in ex vivo experiments to explore which were the best in terms of biocompatibility. In this study we compared the Carmeda system (Medtronic) and the Capiox system (Terumo) with covalent heparin bonding, and the Duraflo-II (Baxter) with ionic heparin bonding, evaluating them in ex vivo experiments. They were primed with fresh human blood, and we studied and compared the platelet counts, fibrinogen, D-dimmer, beta-thioguanine (TG), thrombin-antithrombin complex (TAT), and C3a and C4a of each of them. Additional research will be presented in the future.