title: Biphasic pro-thrombotic and inflammatory responses after coronary artery bypass surgery.
abstract: Early graft failure after coronary artery bypass grafting (CABG) is related to thrombosis and inflammation in the grafted vessel(s). The time courses of, and relationships between, pro-thrombotic and inflammatory responses to CABG surgery have, however, not been well defined. Fifteen patients undergoing CABG were examined before, and 1 h, 1 day, 7 days, and 3 months after surgery. Cellular markers of platelet and leukocyte activation were monitored by whole blood flow cytometry, and plasma markers of pro-thrombotic and inflammatory responses were analyzed by immunoassays. CABG immediately increased circulating P-selectin-positive platelets, leukocyte CD11b expression, and platelet-leukocyte aggregates (PLAs). Thrombin generation (F1 + 2 levels) and cytokine release [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-8, and IL-10], soluble P-selectin, and soluble E-selectin also increased immediately. These alterations persisted during the first week after surgery, with re-bound increases of circulating activated platelets and PLAs, TNF-alpha, and F1 + 2 on day 7. Platelet and PLA responsiveness to in vitro stimulation was suppressed immediately after CABG, but markedly enhanced 1 week after surgery. After 3 months, plasma soluble P-selectin, F1 + 2, and IL-10, and monocyte CD11b expression were still slightly elevated compared with baseline. In conclusion, CABG induces marked pro-thrombotic and inflammatory responses, which persist for at least 1 week. Platelet activation, platelet reactivity, PLA formation, thrombin generation, and TNF-alpha release show a second peak 1 week after surgery. These findings suggest that intensified and prolonged antithrombotic/inflammatory treatment should be considered after CABG surgery.
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden. Nail.Li@ks.se
authors.forename: N
authors.initials: N
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Astudillo
authors.forename: T
authors.initials: T
authors.lastname: Ivert
authors.forename: P
authors.initials: P
authors.lastname: Hjemdahl
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001798:Blood Proteins / Q000032:analysis; D002448:Cell Adhesion; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology*; D007962:Leukocytes / Q000502:physiology; D008297:Male; D015539:Platelet Activation; D019851:Thrombophilia / Q000097:blood / Q000209:etiology*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D016207:Cytokines