Formation of C5a during cardiopulmonary bypass: inhibition by precoating with heparin

A novel enzyme immunoassay based on direct detection of C5a by a monoclonal antibody (C17/5) specific for a neoepitope exposed in C5a/C5adesArg was used to measure in vivo and in vitro C5a formation during cardiopulmonary bypass. In vivo, we observed a significant threefold to fourfold increase in patient plasma C5a/C5adesArg levels from baseline values (5.6; 1.6 to 12.9 ng/mL) (median and range) up to 42 hours postoperatively (17.5; 6.5 to 46.0 ng/mL) when two different uncoated cardiopulmonary bypass circuits were used. Coating of the extracorporeal circuit with end-point-attached heparin completely abolished C5a formation in vitro during circulation of blood through the circuit for 120 minutes. The C5a concentration (median and range) was 3.2 (2.6 to 15.9) ng/mL at the start and 3.1 (2.7 to 15.0) ng/mL at the end of the experiment. In the uncoated setups the corresponding C5a concentrations were 10.1 (6.2 to 17.5) and 19.7 (13.1 to 24.3) ng/mL. Finally, heparin-coated cardiopulmonary bypass circuits were examined in vivo. C5a levels did not increase significantly during the cardiopulmonary bypass period in the heparin-coated group in contrast to the uncoated group, but the postoperative increase in C5a levels was similar in the two groups. We conclude that heparin coating improves biocompatibility by completely abolishing C5a formation in vitro. The discrepancy between the in vitro and the in vivo findings is probably related to the complicated biological turnover of C5a.     

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.     

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.     

Use of heparin-coated cardiopulmonary bypass circuit with low-dose heparin reduces postoperative bleeding.

Postoperative bleeding was examined in patients undergoing cardiopulmonary bypass with a heparin-coated circuit and low-dose heparin. Out of 150 patients who underwent cardiopulmonary bypass for longer than 90 minutes, 74 received a standard dose (300 IU/kg) of heparin with an uncoated circuit (group C) and 76 received a low-dose (150 IU/kg) of heparin with a heparin-coated circuit (group H). The coagulation and fibrinolytic systems were investigated in 24 patients. Re-opening of the chest due to bleeding was performed in 5 patients in group C (7%), but none of the patients in group H (p=0. 03). The median of blood loss in the first 12 hours after surgery was 292 ml in group C, and 216 ml in group H (p=0.006). There were no significant differences in the peak thrombin-antithrombin complex concentration between the two groups. The plasmin-alpha 2 plasmin inhibitor complex concentrations after protamine administration were 1.9 ng/ml (median) in group C and 1.1 ng/ml in group H (p=0.002). The use of heparin-coated cardiopulmonary bypass circuits with low-dose heparin suppressed the activation of fibrinolysis. This may explain the reduction in postoperative bleeding.     

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.     

Effects of Duraflo II heparin-coated cardiopulmonary bypass circuits on the coagulation system, endothelial damage, and cytokine release in patients with cardiac operation employing aprotinin and steroids

The effects of Duraflo II heparin coated cardiopulmonary bypass circuits, low-dose aprotinin, and steroids on the coagulation system, endothelial damage, and cytokine release were evaluated by comparing those treated with low-dose aprotinin and steroids. Twenty-four adult patients undergoing coronary artery bypass grafting, aortic valve replacement, or valve repair surgery were randomly assigned to 2 groups: either heparin-coated (Duraflo group, n = 12) or noncoated equipment (noncoated group, n = 12) groups. In the Duraflo group, the cardiopulmonary reservoir was also coated with heparin. There were no significant differences in age at the time of operation, aortic cross-clamp time, cardiopulmonary bypass time, and rectal temperature during cardiopulmonary bypass. Standard systemic heparinization was performed. Methylpredonisolone and low-dose aprotinin were given in both groups of patients. Serum XIIa factor, TAT, and IL-6 were significantly higher in the control group than in the Duraflo group during cardiopulmonary bypass (p < 0.01). Serum IL-8 was significantly higher in the control group than in the Duraflo group at 24 h after cardiopulmonary bypass (p < 0.05). No significant difference was found in serum thrombomodulin and TNF-alpha; both were within normal during the study period. These results indicate that the use of Duraflo II heparin coated equipment and a heparin-coated cardiopulmonary reservoir suppressed excess coagulation and inflammatory reaction induced by cardiopulmonary bypass.     

Heparin-coated circuits reduce activation of granulocytes during cardiopulmonary bypass. A clinical study.

Activated granulocytes release highly active enzymes such as myeloperoxidase and lactoferrin, which can be involved in tissue destruction mediated by oxygen free radicals. Cardiopulmonary bypass has been reported to activate granulocytes. Bypass circuits coated with heparin have been shown to reduce release of granulocyte factors in experimental studies. In the present study, heparin-coated circuits were compared with noncoated circuits. In seven patients undergoing coronary bypass, heparin-coated circuits were used (group HC), and seven served as control patients (group C). In group HC the heparin dose was reduced to 75% (225 IU/kg). Group C had the standard dose of 300 IU/kg. No preoperative differences in myeloperoxidase and lactoferrin were observed between the groups. At the end of bypass in both groups, there was a significant increase of these enzymes (p less than 0.001) followed by a later decrease. In group HC, however, the release of myeloperoxidase was significantly lower than in group C (215 +/- 24 versus 573 +/- 133 micrograms/L, mean +/- standard error of the mean). The release of lactoferrin was significantly lower in group HC than in group C both at the end of cardiopulmonary bypass (659 +/- 79 versus 1448 +/- 121 micrograms/L) and 3 hours after bypass (224 +/- 37 versus 536 +/- 82 micrograms/L). Granulocytes as well as total number of leukocytes continued to increase until 1 hour after bypass (p less than 0.001) and then manifested a slow decrease. It was concluded that the use of heparin-coated circuits reduced the release of granulocyte factors because of lower activation of leukocytes.     

Use of heparin-bonded circuits in cardiopulmonary bypass improves clinical outcome

OBJECTIVE: The use of heparin-coated surfaces in cardiopulmonary bypass has been shown to decrease the inflammatory response imposed by the contact between blood and artificial surfaces. One would expect this reaction to improve clinical outcome. However, this has been difficult to verify. This investigation is based on an aggregation of two randomized studies from our institution and highlights possible effects of heparin coating on a number of clinically oriented parameters. DESIGN: Departmental analysis of patients subjected to coronary artery bypass surgery using heparin-coated circuits. Cardiopulmonary bypass was employed using either the Carmeda or Duraflo heparin coatings compared with a control. The systemic heparin dose was reduced in the heparin-coated groups (ACT > 250 s) vs control group patients (ACT > 480 s). The effects of heparin coating related to clinical outcome were studied. RESULTS: The use of heparin-coated circuits reduced the mean length of stay in hospital from 7.8 +/- 2.5 to 7.3 +/- 1.8 days (p = 0.040) and postoperative ventilation time from 9.7 +/- 9.2 to 8.2 +/- 8.5 h (p = 0.018), blood loss 8 h post surgery from 676 +/- 385 to 540 +/- 245 ml (p = 0.001), individual perioperative change of haemoglobin loss (p = 0.001), leukocyte count (p = 0.000) and creatinine elevation (p = 0.000), proportion of patients exposed to allogenous blood transfusions 39.2 vs 23.9% (p = 0.001), postoperative coagulation disturbances 4.4 vs 0.4% (p = 0.006), postoperative deviations from the normal postoperative course 47.2 vs 36.7% (p = 0.035), neurological deviations 9.4 vs 3.9% (p = 0.021) and atrial fibrillation 26.4 vs 18.0% (p = 0.041). No effects were found with respect to perioperative platelet count, postoperative fever reaction and 5-year survival. CONCLUSION: Based on several indicators, the use of heparin coating in cardiopulmonary bypass is associated with improved clinical results.     

Platelet activation and aggregation during normothermic cardiopulmonary bypass

OBJECTIVE: The usefulness of heparin-bonded circuits under normothermic cardiopulmonary bypass has not been elucidated. We studied platelet activation and aggregation differences between heparin-bonded and nonheparin-bonded circuits in patients undergoing surgery involving normothermic cardiopulmonary bypass. METHODS: Eight patients underwent coronary artery bypass grafting with non heparin-bonded circuits (controls) and 7 the same with heparin-bonded circuits (heparin group). Heparin bonding was applied to the blood contact surface of our system, including the oxygenator and connecting tubes. Patient body temperature was kept between 36 and 37 degrees C. Beta-thromboglobulin and platelet factor 4 were measured before, during, and after cardiopulmonary bypass, and platelet aggregation was evaluated by laser-light scattering. RESULTS: Changes in beta-thromboglobulin and platelet factor 4 during and after cardiopulmonary bypass were similar in both groups. Small particle formation was the primary aggregate induced during and after cardiopulmonary bypass in both groups, and serial changes in particle formation up to 24 hours after cardiopulmonary bypass were similar in both groups. CONCLUSIONS: Our results indicate that in 2-3 hours of normothermic cardiopulmonary bypass, heparin-bonded circuits are similar to nonheparin-bonded ones in platelet compatibility.     

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

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

'High dose' aprotinin and heparin-coated circuits: clinical efficacy and inflammatory response

Heparin-coated cardiopulmonary bypass circuits reduce the inflammatory response to cardiopulmonary bypass circuit, improve biocompatibility and may protect the postoperative hemostasic mechanisms in routine coronary bypass operations. 'High-dose' aprotinin reduces bloodloss, transfusion needs, and re-explorations as a result of bleeding, and may have an additional role in reducing the inflammatory response of the body to cardiopulmonary bypass circuit. It has not been established, however, if the addition of a heparin-coated circuit to the intraoperative administration of 'high dose' aprotinin further reduces the whole-body inflammatory response to cardiopulmonary bypass circuit and improves the postoperative clinical course of the patients who are undergoing coronary surgery. Thirty patients undergoing primary elective coronary artery bypass grafting were studied. All the patients received, intraoperatively, the serine-protease inhibitor aprotinin according to the 'Hammersmith' protocol and full heparin dose. Patients were randomly allocated to be treated either with a circuit completely coated with surface-bound heparin (n = 15) or with an uncoated, but otherwise identical, circuit (n = 15). Differences in the clinical course of the two groups of patients, as well as differences in the behavior of hematological and inflammatory (interleukin-6 (IL-6) and C-reactive protein) factors before, during and after bypass, were analyzed. There were no significant differences between the two groups in terms of bleeding and transfusional requirements, the time spent on a ventilator, or in duration of stay in the intensive care unit (ICU). In all patients, a significant increase in the total white blood cell count, neutrophils, serum IL-6 and C-reactive protein occurred in relation to cardiopulmonary bypass. This was not influenced by heparin precoating of the circuit. In addition, there was an increase in the monocyte count during follow-up, and there was a trend towards higher monocyte counts in the patients who were treated with heparin-coated circuits. These results suggest that the addition of a heparin-coated circuit to the intraoperative 'high-dose' aprotinin therapy probably had little influence on the clinical course and on the time-course of the inflammatory parameters of the adult patients undergoing primary coronary surgery with a full heparinization protocol.     

Use of Heparin-bonded Circuits in Cardiopulmonary Bypass Improves Clinical Outcome

Objective : The use of heparin-coated surfaces in cardiopulmonary bypass has been shown to decrease the inflammatory response imposed by the contact between blood and artificial surfaces. One would expect this reaction to improve clinical outcome. However, this has been difficult to verify. This investigation is based on an aggregation of two randomized studies from our institution and highlights possible effects of heparin coating on a number of clinically oriented parameters. Design : Departmental analysis of patients subjected to coronary artery bypass surgery using heparin-coated circuits. Cardiopulmonary bypass was employed using either the Carmeda or Duraflo heparin coatings compared with a control. The systemic heparin dose was reduced in the heparin-coated groups (ACT > 250 s) vs control group patients (ACT > 480 s). The effects of heparin coating related to clinical outcome were studied. Results : The use of heparin-coated circuits reduced the mean length of stay in hospital from 7.8 &#45 2.5 to 7.3 &#45 1.8 days ( p = 0.040) and postoperative ventilation time from 9.7 &#45 9.2 to 8.2 &#45 8.5 h ( p = 0.018), blood loss 8 h post surgery from 676 &#45 385 to 540 &#45 245 ml ( p = 0.001), individual perioperative change of haemoglobin loss ( p = 0.001), leukocyte count ( p = 0.000) and creatinine elevation ( p = 0.000), proportion of patients exposed to allogenous blood transfusions 39.2 vs 23.9% ( p = 0.001), postoperative coagulation disturbances 4.4 vs 0.4% ( p = 0.006), postoperative deviations from the normal postoperative course 47.2 vs 36.7% ( p = 0.035), neurological deviations 9.4 vs 3.9% ( p = 0.021) and atrial fibrillation 26.4 vs 18.0% ( p = 0.041). No effects were found with respect to perioperative platelet count, postoperative fever reaction and 5-year survival. Conclusion : Based on several indicators, the use of heparin coating in cardiopulmonary bypass is associated with improved clinical results.     

Antiinflammatory effect of heparin-coated circuits with leukocyte-depleting filters in coronary bypass surgery

Cardiac surgery with cardiopulmonary bypass is associated with a systemic inflammatory response. We examined combined use of heparin coating of the cardiopulmonary bypass circuit and a leukocyte-depleting arterial line filter to reduce this response. Thirty patients were allocated randomly to equal groups with a conventional circuit and arterial line filter (C group), a heparin-coated circuit with a conventional filter (H group), or a heparin-coated circuit with a leukocyte-depleting arterial line filter (HF group). Cytokines and respiratory function were repeatedly measured perioperatively. Plasma interleukin (IL)-6 concentrations in the HF group were lower than in the C group immediately following bypass and operation, at 4 h, and 12 h (p < 0.05). Plasma IL-8 was lower in the HF group than in the C group at 4 h (p < 0.05). The respiratory index was lower immediately after bypass in the HF group than the C group (0.61 +/- 0.2 versus 1.05 +/- 0.4, p < 0.05). Heparin-coated circuits with leukocyte-depleting filters decrease inflammatory responses and improve pulmonary function during operation.     

Percutaneous cardiopulmonary support with heparin-coated circuits in postcardiotomy cardiogenic shock. Efficacy and comparison with left heart bypass.

OBJECTIVE: Percutaneous cardiopulmonary support, a simplified form of venoarterial bypass, using totally heparin-coated circuits, has recently come into clinical use. To clarify its efficacy in postcardiotomy cardiogenic shock to aid weaning from cardiopulmonary bypass, we compared results of percutaneous cardiopulmonary support with those of left heart bypass using a centrifugal pump. METHODS: We reviewed 18 patients treated between 1991 and 1998 who could not be weaned from cardiopulmonary bypass. Nine were aided by totally heparin-coated percutaneous cardiopulmonary support (PCPS group), and 9 supported by left heart bypass using a centrifugal pump (LHB group). In both groups, activated clotting time was controlled at 150-200 seconds using minimal doses of heparin as needed. RESULTS: Weaning and survival rates were higher in the PCPS group than in the LHB group (100% vs 55.6%, and 66.7% vs 22.2%). The PCPS group had a smaller amount of blood loss and needed a smaller amount of blood components in the immediate postoperative period. One percutaneous cardiopulmonary support patient required surgical re-exploration for postoperative bleeding (11.1%), but no clinical thromboembolic event occurred in the PCPS group. In the LHB group, 5 patients underwent surgical re-exploration for postoperative bleeding (55.6%), and 2 underwent thrombus extirpation in the left ventricle (22.2%). CONCLUSIONS: Although this study was retrospective and historical backgrounds could have been involved, our data suggest that totally heparin-coated percutaneous cardiopulmonary support system appears more effective as an aid to weaning from cardiopulmonary bypass and in short-term circulatory support for patients in postcardiotomy cardiogenic shock.     

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)     

Descending thoracic aortic aneurysm repair with the aid of partial cardiopulmonary bypass: heparin-coated circuits versus nonheparin-coated circuits

BACKGROUND: We have performed descending thoracic aortic aneurysm repairs with partial cardiopulmonary bypass, including heparin-coated circuits. The aim of this study was to evaluate (i) the impact of partial cardiopulmonary bypass on distal organ function and surgical outcomes; and (ii) the effectiveness of using heparin-coated circuits for preventing bleeding complications. METHODS: From July 1980 to June 2004, 309 patients underwent descending thoracic aortic aneurysm repairs using partial cardiopulmonary bypass. Their mean age was 61 years (range 19-81 years). One hundred of the 309 patients underwent repair of descending thoracic aortic aneurysm with heparin-coated circuits. Blood data for renal and hepatic function were collected on the day before the operation and postoperative days. RESULTS: The in-hospital mortality was 15%. Distal organ dysfunction included spinal cord dysfunction in 2 patients (0.7%) and renal failure necessitating hemodialysis in 15 patients (5%, 15/297: excluded 12 dialysis patients). Multivariate analyses showed that preoperative hemodialysis and emergency operation were risk factors for operative mortality and that emergency operation was a risk factor for requiring hemodialysis. Renal and hepatic function normalized by 2 weeks after surgery. There were no significant differences between the heparin-coated group and nonheparin-coated group in amounts of packed red cells, fresh frozen plasma, and platelets transfused during the procedures. CONCLUSIONS: Our data showed that partial cardiopulmonary bypass is a safe and effective method for distal perfusion. Using this technique, descending thoracic aortic aneurysm repair can be performed with acceptable mortality and morbidity. However, the superiority of heparin-coated circuits over nonheparin-coated ones was not proved.     

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

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

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.     

A prospective randomized trial of Duraflo II heparin-coated circuits in cardiac reoperations.

BACKGROUND: Heparin-coated circuits in cardiopulmonary bypass have been shown to decrease the systemic inflammatory responses associated with cardiopulmonary bypass. Previous clinical studies on low-risk patients who had coronary artery bypass grafting (CABG) and received full-dose systemic heparin did not have clearly improved clinical outcomes. We hypothesized that the beneficial effects of heparin-coated circuits might be seen in patients who had cardiac reoperations. METHODS: Three hundred fifty patients who had reoperation with CABG only (58%), or with valve operations (42%) were randomly assigned to receive either a heparin-coated (Duraflo II; study group) or uncoated (control group) circuit. Clinical outcomes were compared and the variables were analyzed using the following three groups: entire populations of study group and control group, subgroup of patients who had CABG reoperation only, and a subgroup who had valve reoperation or combined valve and CABG reoperation. RESULTS: Preoperative variables were the same in both groups. No difference in clinical outcomes could be demonstrated except that the percentage of patients with major bleeding episodes was significantly lower in the study group (1.2% versus 5.4%, p = 0.035). In the subgroup analysis of patients who had valve reoperations, lower blood transfusion requirements in the intensive care unit (p = 0.013) were found in the study group. When the subgroup of patients who had CABG reoperations was analyzed separately, there was a trend toward less reoperation for bleeding in the study group (0% versus 4.0%, p = 0.058). CONCLUSIONS: We conclude that the use of heparin-coated circuits was safe and imparted protection from reoperations for bleeding and major bleeding episodes. Material-independent blood activation (eg, blood-air interface and cardiotomy suction) blunted the total effect of the heparin-coated surface.