Aprotinin application has no negative effect on osseous implant integration: a biomechanical and histomorphometric investigation in a rat model

Intraoperative blood loss requiring allogenic blood transfusion (ABT) is a common problem in major orthopedic surgery. Since transfusion related side effects up to fatal consequences due to blood type incompatibility cannot be excluded completely, it is desirable to reduce the amount of blood loss and transfusions to a minimum. Encouraging results in the application of aprotinin, a natural protease-inhibitor with antifibrinolytic, bleeding-reducing properties, in thoracic-, heart- and abdominal surgery led to the use of aprotinin also in orthopedic surgery. One important safety issue in the use of aprotinin in orthopedic surgery is a possible negative effect on the osseous integration of an implant due to the multiple interactions of aprotinin with several enzymatic systems. In this study, we therefore investigated the influence of aprotinin on the osseous ingrowth of a titanium-implant in a rat model. Forty female Sprague–Dawley rats underwent unilateral retrograde nailing of the femur. Animals were divided in two groups, one receiving i.v. aprotinin intraoperatively, the other group receiving the same amount as saline solution. After 56 days animals were killed and from each group half of the femora were prepared for biomechanical testing, the other half for histological examination. The push-out experiment revealed no significant difference between the aprotinin-group and the control-group, both showing comparable shear stresses. In addition, the histomorphometrical analysis showed comparable implant integration between both groups. The results demonstrate that perioperative aprotinin application has no negative effect on osseous implant integration in a rat model. An erratum to this article can be found at