BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY 35, 77-82 (1986) The Effect of Aspirin on Protein Breakdown in Septic Man’ M. MICCOLO,* W. M. NOVICK,” P. L. MARINO,~ AND T. P. STEIN,*.’ *Surgical Research Laboratories, TDepartment of Medicine, Graduate Hospital, and *Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania 19146 Received January 11, 1985 In pathological states associated with hypermetabolism, such as fever, sepsis, and trauma, there is a marked negative nitrogen balance resulting in a reduction in body protein (l-4). Most likely, this is part of the normal adaptive response to stress, with the body rearranging its complement of enzymes to adapt to the stress. But if the loss of protein is prolonged, the ability of the injured patient to recover may be impaired. So there is considerable interest in limiting the extent of the response. It has been suggested that the pathway for this response proceeds via leukocyte pyrogen (LEM), which acts simultaneously on the hypothalamus to produce a febrile state and on muscle to stimulate prostaglandin (PG) release, which then stimulates proteolysis via the lysosomal pathway. The prostaglandin moiety involved is believed to be PGE2 which is derived from arachidonate via the cyclooxygenase reaction. In vitro, the addition of cyclooxygenase inhibitors, such as indomethacin, meclofenamate, and aspirin, leads to decreased proteolysis in incubated muscles derived from septic rats. From these observations, Goldberg and co-workers suggested that cyclooxygenase inhibitors could be used to reduce the negative nitrogen balance in hypercatabolic patients (43). The purpose of this study was to test this hypothesis in vivo in seriously septic patients by using a pharmacological dosage of aspirin as the cyclooxygenase inhibitor. We measured the effect of a single pulse (three 500-mg tablets) of aspirin on the urea production rate as measured by the primed constant infusion of lSN-labeled urea method (6,7). If the aspirin decreased protein breakdown and hence urea production, the “N enrichment of the plasma urea pool should increase since there should be less cold (unlabeled) urea entering the plasma urea pool. We also examined the plasma amino acid levels for changes in the plasma amino acid pattern following the administration of the aspirin. ’ This research was supported by USPHS Grant AM 33415. ’ To whom inquiries should be addressed at the Department of Surgery, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, 401 Haddon Ave., Camden, N.J. 08103. 77 088%4505/86 $3.00 Copyright 0 1986 by Academic Press, Inc. All rights of reproduction in any form reserved.