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(Circulation. 2001;104:I-265.)
© 2001 American Heart Association, Inc.

Thoracic Transplantation and Ventricular Assist Devices

Aprotinin But Not -Aminocaproic Acid Decreases Interleukin-10 After Cardiac Surgery With Extracorporeal Circulation

Randomized, Double-Blind, Placebo-Controlled Study in Patients Receiving Aprotinin and -Aminocaproic Acid

Philip E. Greilich, MD; Kuniyuki Okada, MD; Paige Latham, MD; Ramaswamy Ravi Kumar, MD; Michael E. Jessen, MD

From Dallas Veterans Affairs Medical Center: the Department of Anesthesiology and Pain Management (P.E.G., P.L.), the Department of Physiology (K.O.), and the Department of Cardiovascular and Thoracic Surgery (R.R.K., M.E.J.), University of Texas Southwestern Medical Center, Dallas.

Correspondence to Philip E. Greilich, MD, Anesthesiology and Pain Management Service, Dallas Veterans Affairs Medical Center, 4500 S Lancaster Rd (112A), Dallas, TX 75216. E-mail philip.greilich{at}utsouthwestern.edu

Background— Extracorporeal circulation induces a systemic inflammatory response, which may adversely affect organ function. One manifestation of this response is increased fibrinolysis. Antifibrinolytic drugs such as aprotinin and -aminocaproic acid have been effective in reducing fibrinolysis and blood loss after extracorporeal circulation; however, the effects of antifibrinolytic drugs on proinflammatory and anti-inflammatory mediators are not known. This study examined the effects of aprotinin and -aminocaproic acid on plasma levels of proinflammatory [interleukin-6 (IL-6)] and anti-inflammatory [interleukin-10 (IL-10)] cytokines during and after extracorporeal circulation.

Methods and Results— Seventy-two patients undergoing coronary artery bypass grafting with extracorporeal circulation were randomly assigned in a double-blind study to receive high-dose aprotinin, -aminocaproic acid, or saline placebo. Plasma levels of IL-6 and IL-10 were measured at 5 time points before, during, and after extracorporeal circulation. In all 3 groups, both IL-6 and IL-10 rose significantly after institution of extracorporeal circulation and remained elevated through the first postoperative day. Compared with saline, aprotinin significantly reduced IL-10 (P=0.02) and peak IL-6 (P=0.02) after extracorporeal circulation. In contrast, none of the reductions in IL-6 and IL-10 by -aminocaproic acid achieved statistical significance. Both aprotinin and -aminocaproic acid decreased blood loss compared with saline, but there was no significant difference in the number of patients receiving blood products among the treatment groups.

Conclusions— These data suggest that aprotinin and -aminocaproic acid differ in their effects on the inflammatory response to extracorporeal circulation. Aprotinin but not -aminocaproic acid appears to attenuate the rise in the proinflammatory and anti-inflammatory cytokines IL-6 and IL-10. Further studies will be required to determine if these cytokine alterations translate to changes in clinical outcomes.

Key Words: interleukins • antifibrinolytic agents • aprotinin • extracorporeal circulation • surgery