Complement and granulocyte activation in two different types of heparinized extracorporeal circuits

Abstract

Complement and granulocyte activation were studied in cardiopulmonary bypass circuits completely coated with either end-attached covalent-bonded heparin, the Carmeda BioActive Surface, or with the Duraflo II bonded heparin, in combination with reduced systemic heparinization (activated clotting time > 250 seconds). The control groups were perfused with uncoated circuits and full heparin dose (activated clotting time > 480 seconds). Altogether 67 patients undergoing elective first-time myocardial revascularization were investigated, having extracorporeal perfusion with a Duraflo II coated circuit (n = 17), an identical but uncoated circuit (n = 17), a Carmeda coated circuit (n = 17), or an equivalent uncoated circuit (n = 16). During cardiopulmonary bypass, the C3 activation products C3b, iC3b, and C3c (C3bc) and the terminal SC5b-9 complemented complex increased markedly in all four groups compared with baseline, but significantly less in the two coated groups than in their control groups. Additionally, a significantly lower concentration of C3bc was observed in the Carmeda coated group, with maximal increase of median 28 AU/ml compared with 50 AU/ml in the Duraflo II coated group (p = 0.003). Similarly, in the Carmeda coated group, the maximal increase of terminal complement complex was considerably lower (0.8 AU/ml) than the levels recognized in the Duraflo II coated group (2.4 AU/ml) (p < 0.001). The release of the granulocyte activation myeloperoxidase and lactoferrin increased from the beginning of the operation, with peak levels at the end of bypass. A significant reduction of lactoferrin release was recognized when comparing the coated groups with the control groups. The difference between the two coated groups (Carmeda 228 micrograms/L; Duraflo II 332 micrograms/L; p = 0.05) was marginally significant. For myeloperoxidase, no significant differences were observed between the coated and uncoated groups. In conclusion, both types of heparin-coated circuits reduced complement activation and release of lactoferrin, but the Carmeda circuit proved to be more effective than the Duraflo II equipment.

Inflammatory response to cardiopulmonary bypass using two different types of heparin-coated extracorporeal circuits

“…Using Carmeda equipment, higher amounts of heparin, required to achieve the lower limit of ACT, were associated with a lower increase of SC5b-9. These results are in agreement with those of Moen et al 11 and Ovrum et al 12 It has been reported that heparin leaching into the circulation from the Duraflo II surface (about 10% of the bonded heparin) 13 participates in the anticoagulation during the CPB whereas Carmeda coating is more stable. 14 Although heparin reduces the amplification loop of complement C3 convertase, 15 the multivariate analysis implies that only the engineering of the extracorporeal circuit influenced the maximum values of SC5b-9.…”

“…7,9,10 However, recent comparisons of different commercially available heparin-coated circuits have concluded that the Carmeda equipment (end-point attached covalently bonded heparin + Maxima oxygenator) allows better biocompatibility than the Duraflo II equipment (ionically bonded heparin + Univox oxygenator) through greater reduction of complement and neutrophil activation during CPB. 11,12 Therefore, the aim of this prospective study was to evaluate the impact of the different haemocompatibility provided by either the Carmeda or the Duraflo II equipment in the terminal inflammatory response observed after coronary artery surgery, measuring circulating concentrations of cytokines and adhesion molecules.…”

Strategies to prevent intraoperative lung injury during cardiopulmonary bypass

“…The concept behind heparin coating is to mimic the endothelial surface that contains heparin sulphate [2]. Hence, the main beneficial effects of heparin-coated circuits are considered to be the following two: first, a reduction of complement activation (and mainly of factor C5a) ranging between 25% and 45% [29,30], and second, a reduction of the inflammatory reaction which is thought to be accomplished in two ways: through a reduction of complement activation, and through binding of phospholipase A 2 [31]. Heparin reduces the inflammatory responses especially as far as the actions of platelets, leukocytes, and endothelial cells are concerned [31-34].…”

ECMO Biocompatibility: Surface Coatings, Anticoagulation, and Coagulation Monitoring

“…In addition to covalent linkage, ionic linkage has also been demonstrated, most notably in the Duraflo (Baxter) products. However, the difference between ionic and covalent linkage is the retention of the heparin molecule after blood contact in the covalent bonding versus leaching of the heparin in the ionic linkage [13,14].…”