C L Long

Whole body protein synthesis and catabolism in septic man.

The protein catabolic response to sepsis has been measured in three patients and in two normal subjects using a pulse injections of L-[15N]alanine. In addition, the urea kinetics were measured using a pulse administration of [15N]urea. Several nitrogen models which simulated the metabolic pathways of nitrogen-labeled compounds were tried. Best curve fits and acceptable confidence limits were obtained with a four-pool model containing two metabolic pools and two urea pools. Using this model, synthesis and catabolism rates were calculated for a fast and slow protein turnover pool. The mean daily total protein synthesis rate in the normal was 3.695 g/kg compared to 4.479 g/kg in sepsis. Because all subjects were in negative nitrogen balance, the mean total protein catabolic rate in the normal was 4.379 g/kg, compared to 5.298 g/kg in sepsis. These data suggest an increase in both protein synthesis and catabolism during sepsis.

Urinary excretion of 3-methylhistidine: An assessment of muscle protein catabolism in adult normal subjects and during malnutrition, sepsis, and skeletal trauma

The urinary excretion of 3-methylhistidine (3 MEH) has been shown to be a reliable index of muscle protein breakdown. It is decreased in protein-calorie malnutrition and increased during the hypercatabolic phase of sepsis and thermal trauma. Losses of 3 MEH after moderate to severe skeletal trauma in man and animals are reported as increased or unchanged. To clarify this response, 24 male and 6 female skeletal trauma patients were evaluated for 24 hr urinary losses of 3 MEH, nitrogen and creatinine. Eight of the 24 males also received a catabolic steroid for treatment of a head injury. In addition, 3 male and 1 female septic patients were similarly evaluated. Controls consisted of 10 volunteers on a meat free diet for 4 days and of 8 volunteers who were given only intravenous 5% dextrose in water for 3 days. The 3 MEH excretion for all control males was 3.6 mumole/Kg/day and for females was 2.8 Skeletal trauma produced a 280% increase for the males and a 225% increase for the females. Trauma with steroids caused a 325% increase. Sepsis induced a 227% increase in 3 MEH losses for males and 292% for females during the febrile episode. Creatinine excretion also increased significantly in response to trauma and sepsis but the magnitude of the increase was less than for 3 MEH. This was reflected in the 3 MEH to creatinine molar ratio increase from 0.018 for controls to 0.030-0.040 in sepsis and trauma. Patients with extensive body weight loss showed decreases in 3 MEH and creatinine excretion and a molar ratio similar to controls. The calculated contribution of muscle protein to whole body protein breakdown in the trauma and septic groups showed a twofold increase compared to the control group. The data indicate that the increased muscle protein catabolic response following stress of skeletal trauma and sepsis provides an insight on the origin of the large urinary nitrogen losses following such insults.

The effect of major thermal injury and carbohydrate-free intake on serum triglycerides, insulin, and 3-methylhistidine excretion.

The severely burned patient responds differently to starvation ketosis in the early stage of injury as compared to the normal individual. A similar response has been observed in the patient after skeletal trauma and sepsis. In order to determine the extent of muscle protein contribution and the mechanism(s) involved, 11 burn patients with 35% to 80% BSA burn were resuscitated using carbohydrate-free solutions for 3 days followed by unrestricted intake. Blood was drawn daily and 24-hour urinary nitrogens were determined. Controls consisted of 10 preoperative elective surgical patients and two normal volunteers. The burned patients lost a mean +/- SEM of 17.1 +/- 1.72 g nitrogen per day on the third day. The mean +/- SEM ketone body response on the third day for burned patients was 385 +/- 77 mumol/l compared to 727 +/- 81 mumol/l for control patients. The mean +/- SEM 3-methylhistidine loss for burned patients on the third day was 9.83 +/- 0.82 mumol/kg compared to 3.6 mol/kg for control patients. Insulin levels on the third day of fast were three times the normal group. This insulin increase may be the modulating factor that suppresses excessive fat mobilization. This metabolic response causes a lower plasma ketone level, which may then necessitate the need for continued protein catabolism for glucose production for certain tissues. The protein contribution to the hypercatabolic response as assessed by increased urinary nitrogen losses is in part supported by an increased muscle protein breakdown as indicated by increased 3-methylhistidine excretion.

Glucose metabolism and colorectal carcinoma

We evaluated nine patients with colorectal cancer and six control patients in a postabsorptive state in an attempt to define the effect of cancer on glucose turnover, oxidation, recycling, and resting metabolic expenditures (RME). The glucose kinetics were determined using a double-labeled [U-14C] glucose and [6-3H] glucose, and energy expenditures were measured by indirect calorimetry. In addition, we also measured the same parameters in the cancer patient group on a total parenteral nutrition (TPN)-glucose system on the fourth day before and on the fifth day after removal of tumor. In the postabsorptive state, glucose turnover and oxidation rates were similar in the cancer and control group; however, the mean glucose pool size of the cancer group was 47% larger than the control group and was statistically significant (P = .05). Glucose recycling was also two times the control group and was statistically significant (P = .05). The recycling of glucose, both preoperatively and postoperatively, continued in the face of infused glucose; however, the rate was suppressed compared with the fasting cancer group. Postabsorptive RME of the cancer group did not differ from those predicted by the Harris-Benedict equation. Following a 4-day infusion of TPN-glucose that supplied a mean of two times the patients energy needs, the preoperative cancer group showed a mean increase in RME of 25.6% and a 31.58% increase on the fifth postoperative day of TPN-glucose, presumably due to increased lipogenesis and to a much lesser extent from the increased protein synthesis (4 g positive N balance).(ABSTRACT TRUNCATED AT 250 WORDS)

Net metabolic changes of zinc, copper, nitrogen, and potassium balances in skeletal trauma patients

Zinc, copper, nitrogen, and potassium balances of 10 male skeletal trauma patients were determined over 5-6 days each. Nutrition consisted of electrolyte/glucose and/or blood/blood product infusions. Patients were started on balance studies within 24 hr following injury. Zinc and copper were analyzed by atomic absorption while nitrogen was measured by the microKjeldahl technique and potassium by flame photometry. The mean daily balances for these patients were -1563 micrograms zinc, -266 micrograms copper, -20.0 g nitrogen and -29 mEq potassium for 5 patients receiving electrolyte/glucose infusions and +1273 micrograms zinc, +322 micrograms copper, -12.9 g nitrogen, and -26 mEq potassium for 5 patients receiving blood/blood products in addition to electrolyte/glucose. Routine daily maintenance supplementation of 2 mg zinc and 2 mg copper is recommended for skeletal trauma patients on electrolyte/glucose and those on electrolyte/glucose with blood/blood products intravenous infusions. Further balance studies are necessary to ascertain the level of zinc and copper supplementation needed by skeletal trauma patients receiving different nutritional support.