Preventing the inflammatory response to open-heart surgery: The role of aprotinin and other protease inhibitors

This review discusses the role of protease inhibition in reducing or preventing certain of the deleterious effects of major surgery. The ability of agents such as aprotinin to inhibit bleeding and reduce the need for donor blood transfusions is now well established. What is less well recognized is that aprotinin is not simply an antifibrinolytic but is a polyvalent enzyme inhibitor of many of the enzymes which are involved in inflammatory and hemostatic processes. Inappropriate activation of these pathways is considered to be important in the genesis of the inflammatory response to open-heart surgery. The first part of the article reviews aspects of the inflammatory and hemostatic systems which have a common basis and which utilize proteolytic actions for their control. In the later part of the review, the effect of a period of cardiopulmonary bypass on organ and tissues is discussed together with the effects of protease inhibition to prevent any abnormal or inappropriate response to this stimulus. Consideration of these aspects will hopefully allow a more rational and scientific approach to the uses, possible benefits and perceived or real safety issues following administration of these agents.