Reducing the post-pump syndrome by using heparin-coated circuits, steroids, or aprotinin.
BACKGROUND
Cardiopulmonary bypass (CPB) induces a systemic inflammatory response called 'post-pump syndrome'. As a part of a complex interaction between white cells and vascular endothelium, proinflammatory cytokines IL-6 and IL-8 are part of a phased immune response that is also balanced by anti-inflammatory cytokines such as IL-10. We compared the influence of heparin-coated circuits, steroids, and aprotinin on these cytokines, looking for ways to reduce the syndrome.


METHODS
40 patients with coronary artery disease (CAD) undergoing elective CABG were prospectively studied in four randomized groups of 10. Group A received prednisolone pre- and postoperatively (2 x 250 mg), group B received aprotinin perioperatively (6 Mio. KIU). In group C, heparin-coated circuits ('Bioline' by Jostra) were used and in group D no special measures were taken (controls). Plasma levels of cytokines were measured before and during CPB and until 12 h after surgery using an ELISA technique.


RESULTS
In group A IL-6 was significantly (p<0.05) suppressed in contrast to the control group (A: peak at 4 h, 155 pg/ml vs. control: peak at 8 h, 565 pg/ml). IL-8 was also suppressed (A: peak at 30', 22 pg/ml vs. control: peak at 30', 55 pg/ml). IL-10 level changed first and was markedly upregulated in contrast to the control (A: peak at 30', 1600 pg/ml vs. control: peak at 30', 130 pg/ml; p<0.05). In group B (aprotinin) the cytokine release was similar to group A. Using heparin-coated circuits (group C) also led to a significant (p<0.05) IL-10 upregulation (C: peak at 2 h, 1380 pg/ml) and IL-6 suppression (C: peak at 4 h, 290 pg/ml). IL-8 was not influenced significantly.


CONCLUSIONS
The results show a similar reduction of the inflammatory cytokine release (IL-6 and IL-8 as markers) using early steroid application and aprotinin in high dosage. Heparin coating reduces IL-6 and increases IL-10 release, whereas IL-8 is not affected. Further studies should investigate the effects of a combined application for reducing inflammatory cytokine release and the post-pump syndrome.
Harig
F
F
Center for Cardiac Surgery, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany. harig@herz.uni-erlangen.de
Feyrer
R
R
Mahmoud
F O
FO
Blum
U
U
von der Emde
J
J
D000368:Aged; D007611:Aprotinin / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000295:instrumentation; D020099:Coated Materials, Biocompatible; D001026:Coronary Artery Bypass / Q000009:adverse effects; D003327:Coronary Disease / Q000601:surgery; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use*; D006493:Heparin; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000209:etiology / Q000628:therapy*; D016896:Treatment Outcome
D020099:Coated Materials, Biocompatible; D016207:Cytokines; D005938:Glucocorticoids; D015842:Serine Proteinase Inhibitors; D006493:Heparin; D007611:Aprotinin