HIGH AND LOW HEPARIN DOSE WITH HEPARIN-COATED CARDIOPULMONARY BYPASS - ACTIVATION OF COMPLEMENT AND GRANULOCYTES

Background. Cardiopulmonary bypass with heparin-coated circuits allows reduced amounts of systemic heparin. Heparin inhibits activation of t he complement cascade experimentally, but the effects of different lev els of systemic heparin on activation of complement and granulocytes i n patients have remained unknown. Methods. Fifty-two patients undergoi ng coronary artery bypass procedures were studied. Cardiopulmonary byp ass circuits completely coated with surface-bound heparin were used fo r one group given low-dose heparin (n = 17) (activated clotting time > 250 seconds), and was compared with a second group having normal high- dose heparin (activated clotting time >480 seconds) (n = 18). A third control group was perfused with ordinary uncoated circuits and a full heparin dose (n = 17). Results. During cardiopulmonary bypass, the C3 activation products C3b, iC3b, and C3c increased markedly in all three groups compared with baseline, but significantly less in the two hepa rin-coated groups (high dose, median maximal increase 58 arbitrary uni ts (AU)/mL; low dose, 48 AU/mL) compared with the uncoated control gro up (74 AU/mL) (p < 0.01). The difference between the two coated groups was not significant. Similarly, the maximal increase in terminal SC5b -9 complement complex was considerably lower in the heparin-coated gro ups (high dose, 2.5 AU/mL; low dose, 2.6 AU/mL) compared with the leve l observed in the uncoated control group (5.3 AU/mL) (p < 0.01). The r elease of the granulocyte activation enzymes myeloperoxidase and lacto ferrin increased from the beginning of the operation, with peak levels at the end of cardiopulmonary bypass (p < 0.01). The concentration of lactoferrin was significantly (p < 0.01) reduced in the low heparin d ose group compared with the two other groups receiving normal high hep arin doses, indicating that circulating heparin is an important granul ocyte agonist, acting independently of the presence or absence of hepa rin-coated surfaces. Also for myeloperoxidase a higher level was obser ved in the high heparin dose group. Conclusions. Complement activation was significantly reduced in both heparin-coated groups and was indep endent of the level of systemic heparinization, whereas granulocyte ac tivation was reduced only in patients who received low doses of system ically administered heparin. The results indicate that a moderate redu ction of the systemic heparin dose may be an advantage with regard to improved biocompatibility when using heparin-coated cardiopulmonary by pass circuits.