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.     

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

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

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.     

Heparin-Coated Extracorporeal Circulation with Full and Low Dose Heparinization: Comparison of Thrombin Related Coagulatory Effects

Thrombin related coagulatory effects of a heparin-coated cardiopulmonary bypass system combined with full and low dose systemic heparinization were investigated in a prospective, randomized study in coronary bypass surgery patients. One hundred nineteen patients were divided into 3 groups. Group A (n = 39) had a standard uncoated extracorporeal circulation (ECC) set, and systemic heparin was administered in an initial dose of 400 IU/kg body weight. During ECC activated clotting time (ACT) was maintained at > or =480 s. Group B (n = 42) had the same ECC set completely coated with low molecular weight heparin. Intravenous heparin was given in the same dose as in Group A, and ACT was kept at the same level. Group C (n = 38) had the same coated ECC set as Group B, but intravenous heparin was reduced to 150 IU/kg, and during ECC, ACT was set to be > or =240 s. The same ECC components were used in all 3 groups including roller pumps, coronary suction, and an open cardiotomy reservoir. Thrombin generation as indicated by F1/F2 was significantly elevated at an ECC duration >60 min if heparin-coated ECC combined with low dose systemic heparinization was employed. Complexed thrombin (TAT) was significantly elevated after administration of protamine. Release of D-dimers indicating fibrinolysis was not significantly different between groups. Signs of clinical thromboembolism, i.e., postoperative neurological deficit, occurred in 2 patients in Group A and 1 patient in Group C. We conclude that heparin-coated extracorporeal circulation combined with reduced systemic heparinization intraoperatively leads to significantly increased thrombin generation, but not to increased fibrinolysis.     

Extracorporeal circulation, optimized: a pilot study

We designed a pilot study to assess as primary end point the safety and efficacy of a new phosphorylcholine-coated, closed cardiopulmonary bypass (CPB) system (extracorporeal circulation, optimized [ECC.O], Dideco, Mirandola, Italy). The secondary end point was to compare results with two retrospectively matched cohorts of patients who underwent isolated coronary artery by-pass graft (CAGB) with nonphosphorylcholine-bonded circuits and cardiotomy suction (Group II, n = 32) and off-pump coronary artery by-pass (OPCAB) (Group III, n = 26). In January 2005, 30 patients (Group I) undergoing first-time CABG were assigned to the ECC.O group. Five minutes after CPB, initial hematocrit levels were significantly and consistently highest in Group I relative to Group II (Group I, 29.7 +/- 4.4 vs. Group II, 22.7 +/- 4.1; P < 0.001). Red blood cell transfusion rate was reduced drastically in Group I versus Group II (P < 0.001). High differences were also observed in C-reactive protein levels at 24 h after surgery (Group I vs. Group II-P < 0.001 and vs. Group III-P < 0.001) and at 72-h peak value (Group I vs. Group II-P < 0.001 and vs. Group III-P < 0.001). The routine clinical use of the ECC.O system has been demonstrated to be both clinically safe and efficacious. An intensive training program for surgeons, perfusionists, and anesthesiologists is required.     

The effect of controlled aprotinin administration through cardiotomy suction during cardiopulmonary bypass

Cardiotomy suction enhances inflammation and fibrinolysis during cardiopulmonary bypass (CPB). Aprotinin has been shown to reduce the generalized inflammatory insults associated with CPB. The purpose of this study was to evaluate the effect of Aprotinin administration through cardiotomy suction on the inflammatory and fibrinolytic responses during CPB. A pig model of CPB was utilized including 8 animals divided into control and treatment groups. In the treatment group, Aprotinin was infused into the cardiotomy suction (3000 KIU/min), while the same volume of saline was infused in the control group. D-dimer, platelet count, and IL-8 level were analyzed from systemic and cardiotomy suction. It was found that Aprotinin significantly suppressed the increase in D-dimer levels in the systemic (476.3 +/- 341.2 vs. 1218.8 +/- 281.3 ng/ml, p < 0.05) and the cardiotomy suction (565.0 +/- 192.5 vs. 1875.0 +/- 125.0 ng/ml, p < 0.05). Platelet count fell in both groups during CPB, although the reduction was greater in the control (13.1 +/- 5.1 vs. 37.9 +/- 13.8%, p < 0.05). In addition, IL-8 level in the suction solution was significantly lower in the Aprotinin group (56.5 +/- 18.0 vs. 136.3 +/- 14.8 pg/ml, p < 0.05). In conclusion, this study suggested that Aprotinin treatment of the cardiotomy solution might be an effective way of reducing fibrinolysis, platelet reduction, and inflammation associated with CPB.     

Cardiotomy suction versus red cell spinning during repair of descending thoracic aortic aneurysms

Two consecutive series of patients undergoing repair of descending thoracic and thoracoabdominal aortic aneurysms with partial cardiopulmonary bypass and low systemic heparinization (activated coagulation time: ACT greater than 180 sec) for proximal unloading and distal protection were analyzed. During the surgical procedures, thoracic shed blood was recovered either with a red cell spinning autotransfusion device (n=10) or two pump suckers and Duraflo II heparin surface coated cardiotomy reservoirs (n=10). There were 5/10 acute lesions and 1/10 ruptures for the autotransfusion group versus 5/10 acute lesions and 2/10 ruptures for the cardiotomy group (NS). Extension of aortic resection (range 1-8) was 3.6+/-1.2 for autotransfusion versus 3.5+/-1.4 for cardiotomy suction (NS). Mean number of reimplanted patches for intercostal and visceral reperfusion was 0.3+/-0.6 for autotransfusion versus 0.6+/-1.0 for cardiotomy (NS). Perfusion time was 41+/-17 min for autotransfusion versus 60+/-19 min for cardiotomy (p less than 0.05) and cross clamp time was 33+/-14 min for autotransfusion versus 43+/-17 min for cardiotomy (p less than 0.01). Total heparin dose was for 9500+/-2100 IU for autotransfusion versus 9800+/-1300 IU for cardiotomy (NS). The mean of the lowest ACTs measured during perfusion was 281+/-121 sec for autotransfusion versus 258+/-58 sec for cardiotomy (NS). The total protamine dose given was 7800+/-2100 IU for autotransfusion versus 9700+/-1900 IU for cardiotomy (p less than 0.05). The volume of washed red cells prepared was 3186+/-1318 ml for autotransfusion versus 0 for cardiotomy (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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 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.     

Reduced transfusion requirements with a closed cardiopulmonary bypass system

AIM: The aim of this investigation is to reduce blood transfusion in cardiac surgery patients with preoperative conditions predictive for transfusion requirements. We compared the amount of blood transfused in two groups of patients undergoing cardiopulmonary bypass (CPB) with two different circuit systems. METHODS: Sixty patients undergoing cardiac surgery were randomly assigned to two groups: in group A (N=30) cardiopulmonary bypass was accomplished with an open circuit and in group B (N=30) with a closed circuit. The open circuit consisted of a cardiotomy reservoir, a membrane oxygenator and an arterial line filter, while the closed circuit was made up of a collapsible venous reservoir, a membrane oxygenator, an arterial line filter and a cardiotomy reservoir. The amount of transfused packed red cells in each patient was measured until discharge from the hospital. RESULTS: Groups were similar regarding age, gender, body surface area (BSA), New York Heart Association (NYHA) class and comorbidity risk factors. Moreover, there were no significant differences between groups regarding the type of procedures, CPB and aortic cross-clamp times, total amount of cardioplegia and urinary output during CPB. Priming volume was 1180+/-84 mL (group A) and 760+/-72 mL (group B) (P<0.001). Significant differences in transfusion requirements emerged in the two groups: the total volume of packed red cells transfused for each patient was significantly higher in the open system group compared to the closed system group (717+/-486 mL versus 378+/-364 mL) (P=0.003). Clinical outcomes were similar in both groups. CONCLUSION: In patients with preoperative conditions predictive for the need of transfusions, the use of a closed cardiopulmonary bypass circuit can diminish the amount of transfused blood products.     

New mini-extracorporeal circulation system (ECC.O) is a safe technique in coronary surgery

OBJECTIVES: Cardiopulmonary bypass (CPB) is known to cause the systemic inflammatory reaction after cardiac surgery. New coated and closed loop circuit systems may reduce this inflammation response and improve the surgical outcome. This study was designed to evaluate the safety and efficacy of the mini-extracorporeal circulation system (ECC.O) in CABG patients. DESIGN: Forty patients undergoing elective coronary surgery were randomized into two groups, the ECC.O group and the standard CPB group. Routine hemodynamic monitoring and biochemical measurements were registered according to the hospital practice. RESULTS: The clinical outcome of the patients was similar in both groups. There were no significant differences between the groups in the duration of intubation following surgery, the length of intensive care unit-stay or the total hospital stay. The haemoglobin level was significantly higher (p=0.0069) during and after the perfusion in the ECC.O group. CONCLUSIONS: The ECC.O system can be safely used in CABG patients and it maintains haemoglobin level better than conventional CPB.     

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

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

Perfusing and ventilating the patient's lungs during bypass ameliorates the increase in extravascular thermal volume after coronary bypass grafting

BACKGROUND: To test the hypothesis that bilateral extracorporeal circulation (ECC) (Drew technique) ameliorates the increase in extravascular thermal volume (ETV) observed after conventional cardiopulmonary bypass (CPB) in patients undergoing coronary artery bypass grafting. METHODS: Thirty-four consecutive patients underwent either bilateral ECC (n = 24, additional cannulation of pulmonary artery and left atrium and lungs perfused and ventilated during bypass) or conventional CPB (n = 10, right atrial and aortic cannulation, lungs statically inflated to 4 mbar (0.41 cm H(2)O) with oxygen, 500 mL/min). Determinations of ETV (thermodye dilution technique) and intraoperative fluid balance were made before surgery, at the end of surgery, and 4 hours thereafter. In addition, interleukin (IL)-8, thromboxane B2 (TxB(2)), and endothelin (ET)-1 concentrations were measured in the right atrium and pulmonary vein at specified time points. RESULTS: Comparisons of ETV made at the start of surgery, after aortic declamping, and after termination of ECC, respectively, revealed an increase from 4.8 +/- 0.2 mL/kg (mean +/- SEM) to 6.7 +/- 0.4 mL/kg, and 6.3 +/- 0.3 mL/kg with conventional CPB but ETV remained unchanged at 5.2 +/- 0.3 mL/kg, 5.1 +/- 0.2 mL/kg, and 4.9 +/- 0.3 mL/kg with bilateral ECC. Priming volume (1,580 +/- 10 mL versus 2,213 +/- 77 mL, p < 0.001) and intraoperative fluid balance (+1,955 +/- 233 mL versus +2,654 +/- 210 mL, p < 0.05) were less with conventional CPB. Concentrations of IL-8, TxB(2), and ET-1 were not different between groups. CONCLUSIONS: Despite a significantly greater prime volume and a more positive intraoperative fluid balance, ETV did not change with bilateral ECC but increased with conventional CPB. Thus, using the patient's lungs as an oxygenator during bypass mitigates the increase in extravascular pulmonary fluid.     

The effect of cardiotomy suction on the brain injury marker S100beta after cardiopulmonary bypass

BACKGROUND: An increase of S100beta in serum during cardiopulmonary bypass (CPB) has been interpreted as a sign of brain injury. Cardiotomy suction may cause fat embolization, and its role in the S100beta increase was examined. METHODS: Twenty coronary artery operation patients were randomly assigned to two groups, 10 with suction during CPB to cardiotomy reservoir (CR), 10 to cell saving device (CS). S100beta was measured (immunoassay) in blood from the patients and from cell saving device after processing. In 7 additional patients S100beta was measured in the cell saving device before processing and directly from the wound at sternotomy. RESULTS: Before anesthesia, serum S100beta was 0.03+/-0.06 microg/L. At the end of CPB it was 2.47+/-1.31 microg/L and 0.44+/-0.27 microg/L (CR vs CS; p < 0.001). S100beta was 33+/-12 microg/L in CS reservoir and 42+/-18 microg/L in blood from the wound. CONCLUSIONS: Most serum S100beta after CPB with cardiotomy suction may be of extracerebral origin. S100beta after CPB with cell saving device was the same as after off-pump operation. The interpretation that an increase in S100beta during CPB in patients reflects cerebral injury must be questioned.     

An experimental evaluation of continuous cardiotomy reservoir ultrafiltration

Ultrafiltration has been suggested as a means to reduce the morbidity associated with blood activation. However, the application of ultrafiltration to the highly activated blood of the cardiotomy suction subcircuit has not been investigated. The purpose of this study was to determine whether cardiotomy reservoir ultrafiltration (CRUF) would be effective in altering cytokine levels. Six swine, undergoing 90 min of cardiopulmonary bypass (CPB), were divided into two groups; one group was assigned to receive CRUF (N = 3), the other was to serve as controls and did not receive ultrafiltration (N = 3). Blood samples were analyzed for hematocrit, plasma-free hemoglobin, total protein, interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-alpha). Samples were taken pre-bypass, postheparinization, every 30 min during CPB, post-CPB and postprotamine. All data were analyzed using a one-way analysis of variance (ANOVA), with significance accepted at p < .05. There were no significant differences found between treatment and control groups for plasma-free hemoglobin levels (22.4 +/- 22.2 vs. 14.6 +/- 14.4; 40.1 +/- 26.1 vs. 40.0 +/- 19.3). After 90 min of ultrafiltration, there was a significant decrease in TNF-alpha (261.6 +/- 119.6 vs. 71.8 +/- 11.4; p = .02). Although IL-8 levels decreased from throughout the experiment, concentrations did not reach statistical significance. In conclusion, CRUF can be used without increasing cellular destruction, and can decrease certain cytokine levels. Our results suggest that further clinical studies should be undertaken utilizing this technique with a larger sample size.     

Cell adhesion and tissue factor upregulation in oxygenators used during coronary artery bypass grafting are modified by the Corline Heparin Surface

OBJECTIVE: Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. We investigated the influence of a new heparin surface on the activation of cells retrieved from oxygenators used during coronary artery bypass grafting (CABG). DESIGN: Sixty patients undergoing CABG with CPB were randomly assigned to either uncoated or completely Corline Heparin Surface (CHS)-coated circuits with one of three different levels of systemic heparin: standard, high or low. At end of surgery adhered cells were retrieved from the oxygenators and cell count, tissue factor (TF)- and CD11b-expression on monocytes and monocytic TFmRNA were analysed. RESULTS: The heparin coating of the oxygenator prevented adhesion of granulocytes, monocytes and platelets. TF-expression on monocytes from the oxygenators was significantly higher than on circulating cells in all groups. Monocytes from the uncoated oxygenators showed low levels of TF-expression with high levels of TFmRNA. The coated group with high level of heparin showed higher surface-expression of TF with low levels of TFmRNA. CONCLUSION: The CHS was most biocompatible with the standard level of heparin used during CABG whereas elevation of systemic heparin rather increased the activation and TF upregulation in monocytes from oxygenators.     

Cell Adhesion and Tissue Factor Upregulation in Oxygenators used during Coronary Artery Bypass Grafting are Modified by the Corline Heparin Surface

Objective : Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. We investigated the influence of a new heparin surface on the activation of cells retrieved from oxygenators used during coronary artery bypass grafting (CABG). Design : Sixty patients undergoing CABG with CPB were randomly assigned to either uncoated or completely Corline Heparin Surface (CHS)-coated circuits with one of three different levels of systemic heparin: standard, high or low. At end of surgery adhered cells were retrieved from the oxygenators and cell count, tissue factor (TF)- and CD11b-expression on monocytes and monocytic TFmRNA were analysed. Results : The heparin coating of the oxygenator prevented adhesion of granulocytes, monocytes and platelets. TF-expression on monocytes from the oxygenators was significantly higher than on circulating cells in all groups. Monocytes from the uncoated oxygenators showed low levels of TF-expression with high levels of TFmRNA. The coated group with high level of heparin showed higher surface-expression of TF with low levels of TFmRNA. Conclusion : The CHS was most biocompatible with the standard level of heparin used during CABG whereas elevation of systemic heparin rather increased the activation and TF upregulation in monocytes from oxygenators.     

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.     

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.