In pathological staes associated with hypermetabolism, such as acute sepsis, there is marked negative N balance. It has been suggested that the pathway for this response is via leukocyte pyrogen (interleukin I) acting on cyclooxygenase to stimulate prostaglandin release, which then stimulates proteolysis via the lysosomal pathway. In vitro, cyclooxygenase inhibitors decrease proteolysis in muscle tissue from septic rats. We tested this hypothesis in vivo in severely septic patients by using aspirin as the test cyclooxygenase inhibitor. Septic patients (n = 4) were given a primed, constant infusion (183 mg prime, then 37 mg/hr) of 15N-labeled urea for 6 hr to obtain a blood [15N]urea plateau. Blood samples were taken every 30 min. At 180 min 1500 mg of aspirin was given po. If aspirin inhibited protein breakdown, the plateau level should rise, since less cold urea derived from protein breakdown will enter the urea pool. Aspirin did not cause any change in either the BUN concentration, its 15N enrichment, or any of the plasma amino acids. In conclusion, cyclooxygenase inhibition by aspirin in vivo does not decrease protein breakdown in hypercatabolic septic patients.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism