Artificial gravity maintains skeletal muscle protein synthesis during 21 days of simulated microgravity.

We sought to determine the effects of longitudinal loading (artificial gravity) on skeletal muscle protein kinetics in 15 healthy young males after 21 days of 6 degrees head-down tilt bed rest [experimental treatment (Exp) group: n = 8, 31 +/- 1 yr; control (Con) group; n = 7, 28 +/- 1 yr, means +/- SE]. On days 1 and 21 of bed rest, postabsorptive venous blood samples and muscle biopsies (vastus lateralis and soleus) were obtained during a 1-h pulse bolus infusion protocol (0 min, l-[ring-(13)C(6)]phenylalanine, 35 mumol/kg; 30 min, l-[ring-(15)N]phenylalanine, 35 mumol/kg). Outcome measures included mixed muscle fractional synthesis (FSR) and breakdown rates (FBR). The Exp group experienced 1 h of longitudinal loading (2.5G at the feet) via a short-radius centrifuge during each day of bed rest. Mixed muscle FSR in the Con group was reduced by 48.5% (day 1, 0.081 +/- 0.000%/h vs. day 21, 0.042 +/- 0.000%/h; P = 0.001) in vastus lateralis after 21 days of bed rest, whereas the Exp group maintained their rate of protein synthesis. A similar but nonsignificant change in FSR was noted for the soleus muscle (Exp, -7%; Con, -22%). No changes in muscle protein breakdown were observed. In conclusion, 1 h of daily exposure to artificial gravity maintained the rate of protein synthesis of the vastus lateralis and may represent an effective adjunct countermeasure to combat the loss of muscle mass and functional during extended spaceflight.

Skin nitric oxide and its metabolites are increased in nonburned skin after thermal injuries.

Local and systemic inflammation can lead to progression of burn wounds, converting second- to third-degree wounds or extending the burn to adjacent areas. Previous studies have suggested that the skin is an important site of production of nitric oxide (NO), synthesized by inducible nitric oxide synthase (iNOS) activation after injury. NO increases in burned wounds, but its formation in noninjured skin has not been investigated. We hypothesized that after severe burns, NO and cytotoxic peroxynitrite would increase in noninjured skin. We also tested the hypothesis that BBS-2, a specific inhibitor of iNOS, would impair NO formation after burn. Thirteen female sheep were randomized into burn injury and smoke inhalation (n = 5, group 1), burn and smoke treated with BBS-2 (n = 3, group 2), and sham (saline treatment, no injury) (n = 5, group 3). All the animals, including the sham-injury group, were mechanically ventilated for 48 h. Samples of nonburned skin and plasma were collected from each animal, and levels of NO and its metabolites were evaluated using a NO chemiluminescent detector. Nitrotyrosine and iNOS expression were determined in the skin by Immunoperoxidase staining, and scoring of masked slides (epidermis, hair follicles, vessels, glands, and stroma) was performed. Skin NO and metabolites significantly increased in the burn and smoke injury group, and this was inhibited by BBS-2. Nitrotyrosine expression also increased significantly in the skin of burned animals. BBS-2 prevented the increase of NOx but not the increase of nitrotyrosine expression in skin. Plasma levels of NO increased in burned animals when compared with sham, but this increase was not significant. The increase of NO and its metabolites after burn in noninjured skin is followed by a significant increase in peroxynitrite, a potent cytotoxic mediator.

Postexercise protein metabolism in older and younger men following moderate-intensity aerobic exercise.

Regular aerobic exercise strongly influences muscle metabolism in elderly and young; however, the acute effects of aerobic exercise on protein metabolism are not fully understood. We investigated the effect of a single bout of moderate walking (45 min at approximately 40% of peak O2 consumption) on postexercise (POST-EX) muscle metabolism and synthesis of plasma proteins [albumin (ALB) and fibrinogen (FIB)] in untrained older (n = 6) and younger (n = 6) men. We measured muscle phenylalanine (Phe) kinetics before (REST) and POST-EX (10, 60, and 180 min) using l-[ring-2H5]phenylalanine infusion, femoral arteriovenous blood samples, and muscle biopsies. All data are presented as the difference from REST (at 10, 60, and 180 min POST-EX). Mixed muscle fractional synthesis rate (FSR) increased significantly at 10 min POST-EX in both the younger (0.0363%/h) and older men (0.0830%/h), with the younger men staying elevated through 60 min POST-EX (0.0253%/h). ALB FSR increased at 10 min POST-EX in the younger men only (2.30%/day), whereas FIB FSR was elevated in both groups through 180 min POST-EX (younger men = 4.149, older men = 4.107%/day). Muscle protein turnover was also increased, with increases in synthesis and breakdown in younger and older men. Phe rate of disappearance (synthesis) was increased in both groups at 10 min POST-EX and remained elevated through 60 min POST-EX in the older men. A bout of moderate-intensity aerobic exercise induces short-term increases in muscle and plasma protein synthesis in both younger and older men. Aging per se does not diminish the protein metabolic capacity of the elderly to respond to acute aerobic exercise.

Alteration of hepatic fatty acid metabolism after burn injury in pigs.

BACKGROUND: The primary goal of this study was to investigate hepatic fatty acid (FA) metabolism after severe thermal injury. METHODS: Sixteen pigs were divided into control (n = 8) and burn (n = 8, with 40% full thickness total body surface area burned) groups. Catheters were inserted in the right common carotid artery, portal vein, and hepatic vein for blood sampling. Flow probes were placed around the hepatic artery and portal vein for blood flow measurements. Animals were given pain medication and sedated until the tracer study on day 4 after burn. The pigs were infused for 4 hours with U-13C16-palmitate in order to quantify hepatic FA kinetics and oxidation. RESULTS: Liver triglyceride (TG) content was elevated from 162 +/- 16 (control) to 297 +/- 28 micromol TG/g dry liver wt. (p < .05). Hepatic FA uptake and oxidation were similar between the 2 groups, as were malonyl-coenzyme A (CoA) levels and activities of acetyl-CoA carboxylase and adenosine monophosphate (AMP)-activated protein kinase. In contrast, incorporation of plasma-free fatty acids into hepatic TG was elevated (p < .05) and very low density lipoprotein TG (VLDL-TG) secretion was decreased from 0.17 +/- 0.02 (control) to 0.03 +/- 0.01 micromol/kg per minute in burned pigs (p < .05). CONCLUSIONS: The accumulation of hepatic TG in burned animals is due to inhibition of VLDL-TG secretion and to increased synthesis of hepatic TG. Fatty acids are not channeled to TG because of impaired oxidation.

Reversal of catabolism by beta-blockade after severe burns.

BACKGROUND: The catecholamine-mediated hypermetabolic response to severe burns causes increased energy expenditure and muscle-protein catabolism. We hypothesized that blockade of beta-adrenergic stimulation with propranolol would decrease resting energy expenditure and muscle catabolism in patients with severe burns. METHODS: Twenty-five children with acute and severe burns (more than 40 percent of total body-surface area) were studied in a randomized trial. Thirteen received oral propranolol for at least two weeks, and 12 served as untreated controls. The dose of propranolol was adjusted to decrease the resting heart rate by 20 percent from each patient's base-line value. Resting energy expenditure and skeletal-muscle protein kinetics were measured before and after two weeks of beta-blockade (or no therapy, in controls). Body composition was measured serially throughout hospitalization. RESULTS: Patients in the control group and the propranolol group were similar with respect to age, weight, percentage of total body-surface area burned, percentage of body-surface area with third-degree burns, and length of time from injury to metabolic study. Beta-blockade decreased the heart rates and resting energy expenditure in the propranolol group, both as compared with the base-line values (P<0.001 and P=0.01, respectively) and as compared with the values in the control group (P=0.03 and P=0.001, respectively). The net muscle-protein balance increased by 82 percent over base-line values in the propranolol group (P=0.002), whereas it decreased by 27 percent in the control group (P not significant). The fat-free mass, as measured by whole-body potassium scanning, did not change substantially in the propranolol group, whereas it decreased by a mean (+/-SE) of 9+/-2 percent in the control group (P=0.003). CONCLUSIONS: In children with burns, treatment with propranolol during hospitalization attenuates hypermetabolism and reverses muscle-protein catabolism.

Determinants of blood loss during primary burn excision.

BACKGROUND: Excisional therapy for burn wounds is frequently associated with large operative blood losses. Our objective was to identify patient and operative factors that affect surgical blood loss and determine strategies to minimize hemorrhage. METHODS: Data from 92 consecutive pediatric patients with severe burns (>40% total body surface area) were evaluated. Patient demographics, burn characteristics, operative factors, and clinical course variables were correlated with blood loss. Blood loss at the time of initial total burn excision was determined by a standardized, previously validated method. Data were analyzed sequentially and cumulatively through univariate and cross-sectional multivariate linear regression. RESULTS: Demographic factors that correlated with increased blood loss were older age, male sex, and larger body size. Area of full-thickness (third-degree) burn correlated with blood loss, whereas total burn size did not. High wound bacteria counts (derived from quantitative tissue cultures), total wound area excised, and operative time were the strongest predictors of the volume of operative hemorrhage. Blood loss increased with delay to primary burn excision at a maximum at 5 to 12 days after burn injury. CONCLUSIONS: Early definitive surgical therapy before extensive bacterial colonization and rapid operative excision is a strategy that may decrease operative hemorrhage and transfusion requirements during burn surgical procedures.

Efficacy of a high-carbohydrate diet in catabolic illness.

OBJECTIVE: To determine within the setting of isocaloric, isonitrogenous enteral diets whether a diet that supplies most of its calories from fat or carbohydrate would be most beneficial at limiting muscle protein wasting in catabolic illness. DESIGN: Prospective, randomized, crossover trial. SETTING: Academic pediatric burn unit in tertiary medical center. PATIENTS: Fourteen severely burned (>40% total body surface area) children underwent systemic metabolic and cross-leg muscle protein kinetic studies. INTERVENTIONS: All were treated clinically in a similar manner, including early excision and grafting, antimicrobial therapy, and isocaloric, isonitrogenous enteral nutritional support. Subjects randomly received either a high-carbohydrate enteral diet (3% fat, 82% carbohydrate, 15% protein), or a high-fat enteral diet (44% fat, 42% carbohydrates, 14% protein) for 1 week and then crossed over to the other diet for a second week. MEASUREMENTS AND MAIN RESULTS: On day 5 of each diet, muscle protein kinetics were determined from femoral arterial and venous blood samples during a primed-constant d5-phenylalanine infusion. Indirect calorimetry was used to determine systemic resting energy expenditure and respiratory quotient. The seven boys and seven girls were 7.1 +/- 1.1 (mean +/- sem) years old and suffered burns over 65 +/- 4% of their bodies, with 52 +/- 6% being third-degree burns. Muscle protein degradation markedly decreased (p <.01) with administration of the high-carbohydrate diet. Protein synthesis was unaltered. Endogenous insulin concentrations increased during the high-carbohydrate feeding period. No differences in energy expenditure were seen between study diets. CONCLUSIONS: In severely burned pediatric patients, enteral nutrition supplied predominantly as carbohydrate rather than fat improves the net balance of skeletal muscle protein across the leg. This is attributable to decreased protein breakdown, suggesting a protein-sparing effect of high-carbohydrate feedings.

Surfactant phosphatidylcholine in thermally injured pigs.

OBJECTIVE: To investigate the effect of a thermal injury on pulmonary surfactant phosphatidylcholine kinetics. DESIGN: Random, controlled study. SETTING: University research laboratory. SUBJECTS: Yorkshire swine (n = 8) with and without a 40% total body surface area burn. INTERVENTIONS: A new isotope tracer methodology was used to quantify surfactant phosphatidylcholine kinetics. Four days after burn, [1,2-13C2]acetate and [U-(13)C16]palmitate were infused continuously for 8 hrs to quantify surfactant phosphatidylcholine synthesis, secretion, recycling, and irreversible loss. MEASUREMENTS AND MAIN RESULTS: The total surfactant phosphatidylcholine pool size was reduced from the control value of 2.65 +/- 0.05 to 1.61 +/- 0.08 micromol/g wet lung in burned animals (p <.05), as was the proportional contribution of palmitate to lung surfactant phosphatidylcholine composition. This reduction was associated with a significant decrease in lung dynamic compliance from the control value of 66 +/- 6 to 55 +/- 6 mL/cm H2O for burned pigs (p <.05). The most prominent response of lung phosphatidylcholine kinetics was a decrease in the total lung phosphatidylcholine synthesis from a control value of 12.7 +/- 1.2 to 5.5 +/- 0.3 nmol phosphatidylcholine-bound palmitate x hr(-1) x g of wet lung(-1) in burned animals (p<.05). CONCLUSIONS: Pulmonary phosphatidylcholine content and palmitate composition decrease after burn injury because of a decrease in the rate of phosphatidylcholine synthesis. These responses likely contribute to impaired lung compliance.

The effect of short-term growth hormone treatment on growth and energy expenditure in burned children.

Delays in growth are commonly observed in children who have sustained a severe cutaneous burn. The reasons for this growth delay are not completely known, but in adults, plasma growth hormone (GH) levels have been shown to decrease after thermal injury. If this is also the case in severely burned children, the low GH levels may contribute to their chronic growth delay. We propose that treatment with rhGH may prevent this burn-induced growth delay. Height velocities were measured for up to 2 years after injury in 38 burned children (age 7+/-1 years) with a 64+/-2% total burn surface area (TBSA) burn and a 59+/-3% third-degree burn who received 0.2 mg/kg/day rhGH during hospitalization. These height velocities were compared to 41 burned children (age 8+/-1 years) with a 64+/-3% TBSA burn and a 60+/-3% TBSA third-degree burn who were treated similarly but did not receive rhGH. Height velocities and height percentiles were compared to standard height velocity and percentile nomograms of unburned children. To determine the effect of rhGH on energy requirements, resting energy expenditures (REE) were measured by indirect calorimetry and compared to values calculated from the Harris-Benedict equation. All data are presented as mean+/-S.E.M. No differences in average height percentile could be shown between those receiving GH and controls at admission and 6 months after burn. There was, however, a significant difference (P<0.05) in height velocity during the first 2 years after burn between GH (47th+/-6 percentile) and controls (32nd+/-5 percentile). For rhGH-treated children, the REE was elevated by 34+/-4% versus 35+/-5% for controls. Recombinant human GH, given during acute hospitalization, maintained growth in severely burned children who would otherwise experience a significant growth delay. Treatment with rhGH did not atttenuate their elevated REE.

Attenuation of posttraumatic muscle catabolism and osteopenia by long-term growth hormone therapy.

OBJECTIVE: To determine whether the beneficial effects of growth hormone persist throughout the prolonged hypermetabolic and hypercatabolic response to severe burn. SUMMARY BACKGROUND DATA: The hypermetabolic response to severe burn is associated with increased energy expenditure, insulin resistance, immunodeficiency, and whole body catabolism that persists for months after injury. Growth hormone is a potent anabolic agent and salutary modulator of posttraumatic metabolic responses. METHODS: Seventy-two severely burned children were enrolled in a placebo-controlled double-blind trial investigating the effects of growth hormone (0.05 mg/kg per day) on muscle accretion and bone growth. Drug or placebo treatment began on discharge from the intensive care unit and continued for 1 year after burn. Total body weight, height, dual-energy x-ray absorptiometry, indirect calorimetry, and hormone values were measured at discharge, then at 6 months, 9 months, and 12 months after burn. Results were compared between groups. RESULTS: Growth hormone subjects gained more weight than placebo subjects at the 9-month study point; this disparity in weight gain continued to expand throughout the remainder of the study. Height also increased in the growth hormone group compared with controls at 12 months. Change in lean body mass was greater in those treated with growth hormone at 6, 9, and 12 months. Bone mineral content was increased at 9 and 12 months; this was associated with higher parathormone levels. CONCLUSIONS: Low-dose recombinant human growth hormone successfully abates muscle catabolism and osteopenia induced by severe burn.

Anabolic effects of oxandrolone after severe burn.

OBJECTIVE: To explore the hypothesis that oxandrolone may reverse muscle catabolism in cachectic, critically ill pediatric burn patients. SUMMARY BACKGROUND DATA: Severe burn causes exaggerated muscle protein catabolism, contributing to weakness and delayed healing. Oxandrolone is an anabolic steroid that has been used in cachectic hepatitis and AIDS patients. METHODS: Fourteen severely burned children were enrolled during a 5-month period in a prospective cohort analytic study. There was a prolonged delay in the arrival of these patients to the burn unit for definitive care. This neglect of skin grafting and nutritional support resulted in critically ill children with significant malnutrition. On arrival, all patients underwent excision and skin grafting and received similar clinical care. Subjects were studied 5 to 7 days after admission, and again after 1 week of oxandrolone treatment at 0.1 mg/kg by mouth twice daily or no pharmacologic treatment. Muscle protein kinetics were derived from femoral arterial and venous blood samples and vastus lateralis muscle biopsies during a stable isotope infusion. RESULTS: Control and oxandrolone subjects were similar in age, weight, and percentage of body surface area burned. Muscle protein net balance decreased in controls and improved in the oxandrolone group. The improvement in the oxandrolone group was associated with increased protein synthesis efficiency. Muscle protein breakdown was unchanged. CONCLUSIONS: In burn victims, oxandrolone improves muscle protein metabolism through enhanced protein synthesis efficiency. These findings suggest the efficacy of oxandrolone in impeding muscle protein catabolism in cachectic, critically injured children.

Biobrane improves wound healing in burned children without increased risk of infection.

A synthetic bilaminar membrane used as a skin substitute (Biobrane) has been shown to decrease pain and hospitalization in superficial second-degree burns. Despite these benefits, it has not been utilized universally, particularly in young children, due to a perceived increase in related infections. We propose that when this synthetic membrane is applied to superficial scald burns <25% of the total body surface area (TBSA), decreased healing times are expected without increased risk of infection. Between 1994-1999, 89 children treated within 48 h after receiving superficial partial thickness scald burns covering 5-25% TBSA with no indication of infection were seen at our hospital. Forty-one were assigned randomly to receive treatment with the skin substitute Biobrane and 48 to receive conservative treatment with topical antimicrobials and dressing changes. Comparisons of treatment were made between groups for length of hospitalization, wound healing times, and infectious complications. Children treated with Biobrane or topical antimicrobials were similar in age, race, sex, %TBSA burned, and location of burn. Those receiving Biobrane had shorter hospitalizations and healing times, which was significant for both infants and toddlers and older children. Treatment groups were not different in the use of systemic antibiotics or readmissions for infectious complications. Biobrane was removed in 5.9% of cases for non-adherence. The application of Biobrane within 48 h of superficial burns provides for shorter hospitalizations and faster healing times in children of all ages without increased risk of infection.

Determinants of skeletal muscle catabolism after severe burn.

OBJECTIVE: To determine which patient factors affect the degree of catabolism after severe burn. SUMMARY BACKGROUND DATA: Catabolism is associated with severe burn and leads to erosion of lean mass, impaired wound healing, and delayed rehabilitation. METHODS: From 1996 to 1999, 151 stable-isotope protein kinetic studies were performed in 102 pediatric and 21 adult subjects burned over 20-99. 5% of their total body surface area (TBSA). Patient demographics, burn characteristics, and hospital course variables were correlated with the net balance of skeletal muscle protein synthesis and breakdown across the leg. Data were analyzed sequentially and cumulatively through univariate and cross-sectional multiple regression. RESULTS: Increasing age, weight, and delay in definitive surgical treatment predict increased catabolism (P < .05). Body surface area burned increased catabolism until 40% TBSA was reached; catabolism did not consistently increase thereafter. Resting energy expenditure and sepsis were also strong predictors of net protein catabolism. Among factors that did not significantly correlate were burn type, pneumonia, wound contamination, and time after burn. From these results, the authors also infer that gross muscle mass correlates independently with protein wasting after burn. CONCLUSIONS: Heavier, more muscular subjects, and subjects whose definitive surgical treatment is delayed are at the greatest risk for excess catabolism after burn. Sepsis and excessive hypermetabolism are also associated with protein catabolism.

Glucose effects on lung surfactant kinetics in conscious pigs.

The primary goal of this study was to investigate the effects of glucose infusion on surfactant phosphatidylcholine (PC) metabolic kinetics in the lungs. A new stable isotope tracer model was used in which [1,2-(13)C(2)]acetate and uniformly labeled [U-(13)C(16)]palmitate were infused in 12 normal overnight-fasted pigs to quantify lung surfactant kinetics with or without glucose infusion (24 mg. kg(-1). min(-1)). With glucose infusion, the rate of surfactant PC incorporation from de novo synthesized palmitate increased from the control value of 2.1 +/- 0.2 to 15.5 +/- 1.9 nmol PC-bound palmitate. h(-1). g wet lung(-1) (P < 0.05), whereas the incorporation rate from plasma preformed palmitate decreased from the control value of 20.9 +/- 1.9 to 11.6 +/- 1.1 nmol palmitate. h(-1). g wet lung(-1) (P < 0.05). The palmitate composition in lamellar body surfactant PC increased from the control value of 61.7 +/- 2.1% to 75.9 +/- 0.6% (P < 0.05). The surfactant PC secretion rate decreased from the control value of 239.0 +/- 26.1 to 81.9 +/- 5.3 nmol PC-bound palmitate. h(-1). g wet lung(-1) (P < 0.05). We conclude that, whereas surfactant secretion was inhibited by glucose infusion, neither total surfactant PC synthesis nor the surfactant PC pool size was significantly affected due to an increased reliance on de novo synthesized fatty acids.

Persistence of muscle catabolism after severe burn.

BACKGROUND: The hypermetabolic response to severe burn is characterized by muscle protein catabolism. Current opinion states that the hypermetabolic state resolves soon after complete wound closure. Clinically, we have witnessed that burned children appear to be hypermetabolic and catabolic long after full healing of their wounds. Our goal in this study was to determine scientifically if burn-associated hypermetabolism persists after full wound healing. METHODS: To determine the duration of muscle catabolism and systemic hypermetabolism after severe burn in children, patients with > 40% total body surface area burns were enrolled in a prospective, longitudinal study; resting energy expenditure was measured by indirect calorimetry, muscle protein kinetics were determined by using stable isotopic methodology, and body composition was measured by dual-energy x-ray absorptiometry imaging. Data were collected at 6, 9, and 12 months after injury. RESULTS: The mean total body surface area burned was 65% +/- 13%, and the mean age was 7.6 +/- 1. 5 years. Resting energy expenditure was elevated above the predicted age-matched levels from the Harris-Benedict equation and incrementally declined throughout the 12-month study. The net protein balance and lean mass reflected catabolic persistence at 6 and 9 months after severe burn. Between 9 and 12 months, protein breakdown decreased, net protein balance improved, and lean body mass increased. CONCLUSIONS: In severely burned children, hypermetabolism and catabolism remain exaggerated for at least 9 months after injury. This suggests that therapeutic attempts to manipulate the catabolic and hypermetabolic response to severe injury should be continued long after injury.

Palm computer demonstrates a fast and accurate means of burn data collection.

Manual biomedical data collection and entry of the data into a personal computer is time-consuming and can be prone to errors. The purpose of this study was to compare data entry into a hand-held computer versus hand written data followed by entry of the data into a personal computer. A Palm (3Com Palm IIIx, Santa, Clara, Calif) computer with a custom menu-driven program was used for the entry and retrieval of burn-related variables. These variables were also used to create an identical sheet that was filled in by hand. Identical data were retrieved twice from 110 charts 48 hours apart and then used to create an Excel (Microsoft, Redmond, Wash) spreadsheet. One time data were recorded by the Palm entry method, and the other time the data were handwritten. The method of retrieval was alternated between the Palm system and handwritten system every 10 charts. The total time required to log data and to generate an Excel spreadsheet was recorded and used as a study endpoint. The total time for the Palm method of data collection and downloading to a personal computer was 23% faster than hand recording with the personal computer entry method (P < 0.05), and 58% fewer errors were generated with the Palm method.) The Palm is a faster and more accurate means of data collection than a handwritten technique.

Anabolic effects of insulin-like growth factor in combination with insulin-like growth factor binding protein-3 in severely burned adults.

BACKGROUND: The purpose of this study was to determine the anabolic effects of recombinant human insulin-like growth factor-I (rhIGF-1) complexed with its principal binding protein IGF-1 binding protein-3 (IGFBP-3) in severely burned adults. METHODS: Ten burned adults were studied consecutively after receiving saline (pretreatment), then rhIGF-1/IGFBP-3 (treatment) for 5 days. Doses were 1, 2, and 4 mg/kg per day. Glucose, electrolytes, hormones, and leg muscle protein metabolism were determined. Nine other studies were performed on similarly injured adults at comparable times to the treatment studies to control for time effects. RESULTS: Serum IGF-1 and IGFBP-3 levels increased with all doses, but no incremental increases were found. Leg protein balance improved with rhIGF-1/IGFBP-3, which was associated with an increase in muscle protein fractional synthetic rate. These effects were independent of time. All patients were euglycemic without electrolyte imbalances. CONCLUSION: Net protein synthesis in the isolated leg of severely burned adults improved with rhIGF-1/IGFBP-3 without development of glucose abnormalities.

Lung surfactant kinetics in conscious pigs.

The primary goal of this study was to determine the contributions of plasma free fatty acids (FFA) and de novo synthesized fatty acids (FA) to lung surfactant phosphatidylcholine (PC) synthesis. A new stable isotope tracer model was developed in which [1, 2-(13)C(2)]acetate and uniformly labeled [U-(13)C(16)]palmitate were infused in nine normal overnight fasted pigs to quantify surfactant kinetics in the basal state and during low-dose glucose infusion (2 mg. kg(-1). min(-1)). There was no effect of glucose; therefore, all data were pooled. The surfactant PC-bound palmitate incorporation rate from plasma palmitate was 20.9 +/- 1.9 nmol palmitate. h(-1). g wet lung(-1), compared with the rate of 2.1 +/- 0.3 nmol palmitate. h(-1). g wet lung(-1) from de novo synthesized palmitate. The PC-bound palmitate secretion rate from the lamellar body pool to the alveolar surface pool was 239 +/- 26 nmol palmitate. h(-1). g wet lung(-1). Approximately 90% of the secreted PC recycled back to the lamellar bodies for reutilization. We conclude that plasma is the primary contributor of FA for surfactant PC synthesis under the conditions of this experiment.

Muscle protein catabolism after severe burn: effects of IGF-1/IGFBP-3 treatment.

OBJECTIVE: To determine the effects of recombinant human insulin-like growth factor-1 (IGF-1) complexed with its principal binding protein, IGFBP-3, on skeletal muscle metabolism in severely burned children. SUMMARY BACKGROUND DATA: Severe burns are associated with a persistent hypermetabolic response characterized by hyperdynamic circulation and severe muscle catabolism and wasting. Previous studies showed that nutritional support and pharmacologic intervention with anabolic agents such as growth hormone and insulin abrogated muscle wasting and improved net protein synthesis in the severely burned. The use of these agents, however, has several adverse side effects. A new combination of IGF-1 and IGFBP-3 is now available for clinical study. METHODS: Twenty-nine severely burned children were prospectively studied before and after treatment with 0.5, 1, 2, or 4 mg/kg/day IGF-1/IGFBP-3 to determine net balance of protein across the leg, muscle protein fractional synthetic rates, and glucose metabolism. Another group was studied in a similar fashion without IGF-1/IGFBP-3 treatment as time controls. RESULTS: Seventeen of 29 children were catabolic before starting treatment. The infusion of 1.0 mg/kg/day IGF-1/IGFBP-3 increased serum IGF-1, which did not further increase with 2.0 and 4.0 mg/kg/day. IGF-1/IGFBP-3 treatment at 1 to 4 mg/ kg/day improved net protein balance and increased muscle protein fractional synthetic rates. This effect was more pronounced in catabolic children. IGF-1/IGFBP-3 did not affect glucose uptake across the leg or change substrate utilization. CONCLUSIONS: IGF-1/IGFBP-3 at doses of 1 to 4 mg/kg/day attenuates catabolism in catabolic burned children with negligible clinical side effects.

Insulin but not growth hormone stimulates protein anabolism in skin wound and muscle.

We have measured protein kinetics in the scalded skin and normal muscle in anesthetized rabbits. On the 7th day after ear scald, L-[ring-13C6]phenylalanine was infused as a tracer, and the ear and hindlimb were used as arteriovenous units to reflect skin and muscle protein kinetics. Insulin was infused at 0.6 or 2.3-3.4 mU. kg-1. min-1 in the low-dose and high-dose insulin groups. In the growth hormone group, recombinant human growth hormone was administered at 2 mg. kg-1. day-1 after the ear was scalded. The results were compared with a control group in which the ear was scalded but otherwise was not treated. In the control group, net protein loss in the scalded skin and muscle was 23.1 +/- 21.4 and 3.9 +/- 1.5 micromol. 100 g-1. h-1, respectively. Insulin infusion at either high or low dose reduced net protein loss to near zero by inhibiting proteolysis. In contrast, growth hormone treatment had no anabolic effect on either tissue. In conclusion, insulin but not growth hormone has an anabolic effect on scalded skin and normal muscle; low-dose insulin is as effective in achieving an anabolic effect on both tissues, with less hypoglycemic response than high-dose insulin.