title: Effects of epsilon-aminocaproic acid and aprotinin on leukocyte-platelet adhesion in patients undergoing cardiac surgery.
abstract: BACKGROUND
  The administration of aprotinin during cardiopulmonary bypass (CPB) is hypothesized to decrease activation of leukocytes and platelets and possibly reduce their adhesion. Although epsilon-aminocaproic acid (EACA) shares the ability of aprotinin to inhibit excessive plasmin activity after CPB, its effect on leukocyte and platelet activation and leukocyte-platelet (heterotypic) adhesion is largely unknown. This study was performed to determine the relative effectiveness of the antifibrinolytics, aprotinin and EACA, at reducing leukocyte and platelet activation and leukocyte-platelet conjugate formation in patients undergoing CPB.
  
  
  METHODS
  Thirty-six patients scheduled to undergo cardiac surgery with CPB were randomized in a double-blind fashion to receive EACA, aprotinin, or saline (placebo). Markers of plasmin activity (D-dimer concentrations), platelet activation (CD62P), leukocyte activation (CD11b), and leukocyte-platelet adhesion (monocyte- and neutrophil-platelet conjugates) were measured before, during, and after CPB.
  
  
  RESULTS
  Platelet CD62P (P-selectin), monocyte CD11b, and monocyte-platelet conjugates were all significantly increased (compared with baseline) in the saline group during and after CPB. Despite equivalent reductions in D-dimer formation in patients receiving EACA (P < 0.0001) and aprotinin (P < 0.0001), decreases in platelet CD62P and monocyte CD11b expression were incomplete (not significantly different from saline control). In contrast, peak monocyte-platelet conjugate formation was significantly reduced by both EACA (P = 0.026) and aprotinin (P = 0.039) immediately after CPB.
  
  
  CONCLUSIONS
  EACA seems to be as effective as aprotinin at reducing peak monocyte-platelet adhesion after CPB. Furthermore, inhibition of excessive plasmin activity seems to influence monocyte-platelet adhesion. The findings suggest that monocyte-platelet conjugate formation may be a useful marker of monocyte and platelet activation in this clinical setting.
authors.affiliation: Department of Anesthesiology & Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-8894, USA. philip.greilich@utsouthwestern.edu
authors.forename: Philip E
authors.initials: PE
authors.lastname: Greilich
authors.forename: Chad F
authors.initials: CF
authors.lastname: Brouse
authors.forename: Christine S
authors.initials: CS
authors.lastname: Rinder
authors.forename: Brian R
authors.initials: BR
authors.lastname: Smith
authors.forename: Bernardo A
authors.initials: BA
authors.lastname: Sandoval
authors.forename: Henry M
authors.initials: HM
authors.lastname: Rinder
authors.forename: Robert C
authors.initials: RC
authors.lastname: Eberhart
authors.forename: Michael E
authors.initials: ME
authors.lastname: Jessen
mesh_terms: D000368:Aged; D015119:Aminocaproic Acid / Q000494:pharmacology*; D000933:Antifibrinolytic Agents / Q000494:pharmacology*; D007611:Aprotinin / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
chemical_list: D000933:Antifibrinolytic Agents; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin; D015119:Aminocaproic Acid