title: Activation of fibrinolysis in the pericardial cavity after cardiopulmonary bypass.
abstract: Aprotinin is frequently administered systemically in patients undergoing cardiopulmonary bypass to preserve platelet function and ameliorate excessive activation of fibrinolysis. More recently, aprotinin topically applied in the pericardial cavity was also found to improve postoperative blood loss. However, platelet activation was not reduced locally during surgery. Hence, we investigated in the present prospective, in a randomized double-blind trial, the intra- and early postoperative state of systemic and local fibrinolytic activity, and whether topically administered aprotinin acts as an antifibrinolytic and therefore improves local hemostasis. Patients undergoing elective coronary artery bypass grafting were divided in two groups containing 22 patients each. Both, group I and II patients received high-dose aprotinin (6.0 x 10(6) kallikrein inhibitor units (KIU)) systemically. Before resuming extracorporeal circulation (ECC), either 1.0 x 10(6) KIU aprotinin (group I) or vehicle solution (group II) was applied into the pericardial cavity. Plasminogen, 2 alpha(2)-antiplasmin, plasmin-alpha(2)-antiplasmin complex, plasminogen-activator-inhibitor type-1 and D-dimers were measured in the pericardial cavity and systemic circulation immediately before resuming extracorporeal circulation (ECC), and at 1 h and 4 h postoperatively. The local fibrinolytic activity was found to significantly exceed that measured in the systemic circulation over time, whether ot not they received aprotinin into the thoracic wound surface. Furthermore, evidence was provided that topically applied aprotinin reduces not only the local fibrinolytic activity but also the postoperative blood loss significantly by 33% which demonstrates the clinical relevance. The local activation of fibrinolysis seems to play an important role in blood loss after cardiopulmonary bypass. Therefore in fibrinolysis and blood coagulation the surgeon should not only consider what happens in the systemic circulation but also on a local level.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, University Hospital Eppendorf, University of Hamburg, Germany. philipe.khalil@ch-i.med.uni-muenchen.de
authors.forename: Philipe N
authors.initials: PN
authors.lastname: Khalil
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ismail
authors.forename: Peter
authors.initials: P
authors.lastname: Kalmar
authors.forename: Georg
authors.initials: G
authors.lastname: von Knobelsdorff
authors.forename: Guy
authors.initials: G
authors.lastname: Marx
mesh_terms: D000368:Aged; D000933:Antifibrinolytic Agents / Q000494:pharmacology; D007611:Aprotinin / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D001775:Blood Circulation; D016063:Blood Loss, Surgical / Q000517:prevention & control; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003326:Coronary Circulation; D004311:Double-Blind Method; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D007430:Intraoperative Care; D008297:Male; D008875:Middle Aged; D010496:Pericardium; D016896:Treatment Outcome
chemical_list: D000933:Antifibrinolytic Agents; D015415:Biomarkers; D007611:Aprotinin