title: The effects of Carmeda Bioactive Surface on human blood components during simulated extracorporeal circulation.
abstract: Postoperative morbidity after cardiopulmonary bypass most commonly manifests as bleeding diatheses or pulmonary dysfunction. The pathophysiology has been attributed to the activation of cellular and humoral components of blood after contact with an artificial surface. Development of a surface that would be nonthrombogenic and also would constitute a less potent inflammatory stimulus would therefore be beneficial. In the following experiments, we evaluated the heparin-bonded Carmeda Bioactive Surface (Medtronics Cardiopulmonary, Anaheim, Calif.) in an in vitro model of extracorporeal circulation at standard-dose heparin (5 U/ml), to examine the effects of the surface treatment on activation of blood elements, and at reduced-dose heparin (1 U/ml), to determine whether surface-bound heparin would serve as an effective anticoagulant. During the initial recirculation period, platelet counts in the Carmeda (n = 12) circuits were preserved at both doses of heparin and compared with control values (n = 12): At 5 U/ml, control 36% +/- 4% (mean +/- standard error of the mean) versus Carmeda 81% +/- 5%; at 1 U/ml, 43% +/- 3% versus 61% +/- 10%, expressed as a percent of baseline at 30 minutes, p < 0.05. Furthermore, plasma levels of platelet factor 4 and beta-thromboglobulin were significantly reduced in the Carmeda circuits throughout the experiment: At heparin 5 U/ml, 2500 +/- 340 ng/ml versus 604 +/- 191 ng/ml; at 1 U/ml, 2933 +/- 275 ng/ml versus 577 +/- 164 ng/ml of platelet factor 4 at 2 hours (p < 0.05). The pattern of beta-thromboglobulin release was similar, with effects more pronounced at the lower dose of heparin. Surface modification also reduced leukocyte depletion (p < 0.05) and release of elastase at both concentrations of heparin (5 U/ml, 0.72 +/- 0.29 ng/ml versus 0.33 +/- 0.23 ng/ml; 1 U/ml, 0.85 +/- 0.08 ng/ml versus 0.20 +/- 0.05 ng/ml, at 2 hours, p < 0.05). Moreover, as heparin concentration was reduced, Carmeda surface treatment significantly decreased generation of C3a des Arg (1 U/ml, 14,410 +/- 3558 ng/ml versus 3053 +/- 1039 ng/ml at 2 hours, p < 0.05). Although heparin bonding was originally intended to obviate the need for systemic heparinization, Carmeda treatment did not reduce fibrinopeptide A generation at the lower dose of heparin. In summary, Carmeda treatment failed to exhibit anticoagulant efficacy in this model; however, the data suggest that surface modification may have a role in ameliorating the typical inflammatory response initiated by blood contact with an artificial surface.
authors.affiliation: Department of Surgery, Temple University Health Sciences Center, Philadelphia, PA 19140, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Korn
authors.forename: C A
authors.initials: CA
authors.lastname: Fisher
authors.forename: E R
authors.initials: ER
authors.lastname: Livingston
authors.forename: N
authors.initials: N
authors.lastname: Stenach
authors.forename: S J
authors.initials: SJ
authors.lastname: Fishman
authors.forename: V
authors.initials: V
authors.lastname: Jeevanadam
authors.forename: V P
authors.initials: VP
authors.lastname: Addonizio
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000502:physiology*; D003167:Complement Activation / Q000502:physiology; D015926:Complement C3a / Q000032:analysis; D005112:Extracorporeal Circulation / Q000295:instrumentation*; D005344:Fibrinopeptide A / Q000032:analysis; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007958:Leukocyte Count; D019272:Leukocyte Elastase; D007962:Leukocytes / Q000502:physiology*; D010196:Pancreatic Elastase / Q000032:analysis; D010974:Platelet Aggregation; D010978:Platelet Factor 4 / Q000032:analysis; D013929:Thromboxane B2 / Q000032:analysis; D001620:beta-Thromboglobulin / Q000032:analysis
chemical_list: D000925:Anticoagulants; D001620:beta-Thromboglobulin; D005344:Fibrinopeptide A; D010978:Platelet Factor 4; D013929:Thromboxane B2; D015926:Complement C3a; D006493:Heparin; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase