Cancer reduces the metabolic response of muscle to surgical stress in the rat

The metabolic response to surgical stress is characterized by muscle protein breakdown and mobilization of amino acids, e.g., glutamine, from peripheral tissue to visceral organs. Cancer is related to increased protein breakdown of muscle which may influence the normal metabolic response after surgery. The aim was to study the effects of cancer on postoperative peripheral muscle protein and glutamine turnover. Methylcholanthrene-induced sarcomas were implanted subcutaneously in female Lewis rats. Tumor-bearing rats were studied when the tumor was 5-15% of body weight. Control rats were sham implanted. Hysterectomy was performed in control and tumor-bearing rats as a standardized operative procedure. On the second postoperative day a primed constant infusion of para-aminohippuric acid, L-[2,6-H-3]phenylalanine, and L-[3,4-H-3]glutamine was given under ether anesthesia. At steady state, hindquarter muscle protein turnover and glutamine kinetics were determined in a three-compartment model. In control rats muscle protein synthesis almost doubled and protein breakdown increased threefold after hysterectomy, with concomitant increased outward amino acid membrane transport rates. Hysterectomy did not change protein synthesis or breakdown rates in tumor-bearing rats. Muscle glutamine production and membrane transport and release increased after hysterectomy in control rats. Tumor-bearing rats had depressed membrane transport rates and showed no surgical stress response related to muscle glutamine metabolism. The present study shows that surgical stress induces an increased mobilization of amino acids, e,g., glutamine, from muscle that does not occur in the cancer-bearing state. The reduced metabolic response to surgery in the cancer-bearing host may be of particular importance for the functioning of visceral organs, which use amino acids like glutamine at a high rate after trauma. (C) 1998 Academic Press.