Physical Injury and Its Effects on Protein Metabolism

Cuthbertson, D. P.

doi:10.1016/b978-1-4832-3210-2.50016-9

Cited by 38 publications

(15 citation statements)

References 79 publications

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“…The organism reacts to surgery with a non-specific metabolic response [1][2][3][4][5][6]. This stress response is maintained over several days, depending on the severity of the insult.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic and proteomic analysis of liver and muscle alterations caused by surgical stress in rats

López-Hellı́n¹,

Gonzalo²,

Tejeda³

et al. 2005

Clinical Science

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The metabolic response to injury includes major alterations in protein metabolism; however, little is known about alterations in the synthesis of individual proteins and their role in the stress response. Our aim was to study how individual proteins in liver and muscle are altered by abdominal surgery. Changes produced in mRNA and proteins by abdominal surgery were studied in rats using RAP (random arbitrary priming)-PCR, to investigate mRNA alterations, and standard or isotopic (with in vivo radioactive labelling of proteins) two-dimensional electrophoresis/MS proteomic analyses, to study differential expression of proteins. Many of the differentially expressed proteins identified in blood were specifically synthesized by the liver to participate in the stress response. The hepatic proteins (antioxidant proteins, serine protease inhibitors, acute-phase proteins and transport proteins) were secreted into the bloodstream to produce a systemic action, indicating the central role of the liver in the stress response. Overexpressed proteins identified in liver were associated with the glycolytic processes and the folding of nascent proteins, confirming the high metabolic activity of the liver after surgery. The role of skeletal muscle protein as an amino acid donor to fuel the processes involved in the stress response was shown by the decrease in high-molecular-mass myofibrillar proteins. Combined use of the three techniques studied, differential RAP-PCR and standard and isotopic proteome analysis, provided complementary information on the differentially expressed proteins in a rat model of surgical stress.

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“…The organism reacts to surgery with a non-specific metabolic response [1][2][3][4][5][6]. This stress response is maintained over several days, depending on the severity of the insult.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic and proteomic analysis of liver and muscle alterations caused by surgical stress in rats

López-Hellı́n¹,

Gonzalo²,

Tejeda³

et al. 2005

Clinical Science

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“…The alteration that classically defines the metabolic response to the surgery is whole-body net protein catabolism, manifested as negative nitrogen balance (Cuthberson, 1964;Munro, 1964;James, 1981;Waterlow, 1995). The earliest models explaining protein metabolism after injury attributed the protein loss during the flow phase to decreases in protein synthesis (James, 1981).…”

Section: Introductionmentioning

confidence: 99%

Nutritional modulation of protein metabolism after gastrointestinal surgery

et al. 2007

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Background: The metabolic response to surgery includes alterations in protein metabolism, resulting in a net loss of proteins. Protein hypercatabolism is considered an unavoidable consequence of injury, and an important source of morbidity and mortality. Our purpose was to determine the effect of nutrition on protein metabolism following gastrointestinal surgery, and to elucidate whether postoperative protein loss can be prevented with adequate nutritional support. Methods: Patients who had undergone gastrointestinal surgery were given four different parenteral nutritions with increasing glucose, lipid and amino acid content during the 7 days following surgery. Nitrogen balance, protein synthesis and protein breakdown were determined using in vivo stable isotope labelling. Other metabolites (3-methylhistidine, creatinine, urea, cortisol, glucose, insulin, amino acids and C-reactive protein) were measured. Results: A nutrition-dependent alteration of protein metabolism was found in response to surgical injury. Nutrition modified nitrogen balance, whole-body protein breakdown and, to a lesser extent, whole-body protein synthesis and muscle protein breakdown. The low-energy parenteral nutrition without amino acids produced a negative nitrogen balance (postoperative day 7 ¼ À0.381 g protein kg À1 day À1 ) and important alterations in postoperative protein metabolism that did not normalize during the study period (day 7 protein synthesis ¼ 239% and protein breakdown 217% vs preoperative). Patients receiving the two low energy parenteral nutritions containing amino acids had a less negative nitrogen balance (day 7 ¼ À0.011 and À0.133 g protein kg À1 day À1 ) and a transient increase in protein metabolism. The complete parenteral nutrition maintained, during all studied days, protein metabolism parameters within the preoperative reference range (synthesis day 2 ¼ 92%, day 4 ¼ 110% day 7 ¼ 79%; breakdown day 2 ¼ 85%, day 4 ¼ 80%, day 7 ¼ 76% vs preoperative) and a positive nitrogen balance (day 2 ¼ þ 0.0387, day 4 ¼ þ 0.578 and day 7 ¼ þ 0.227 g protein kg À1 day À1 ). Conclusion: Complete nutritional support can prevent protein loss after gastrointestinal surgery and maintain protein metabolism without alterations.

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“…Cuthbertson 1964, Batstone et al 1974, Kinney 1976). Many studies have been directed to finding a means to minimise the loss of body nitrogen following severe trauma.…”

Section: Introductionmentioning

confidence: 99%

The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone

Fürst

1998

Journal of Endocrinology

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The anti-catabolic efficacy of IGF-I treatment commencing before, with or after the onset of catabolism was compared in order to test whether earlier treatment can more effectively blunt a catabolic response. Young rapidly growing male rats (145 g body weight) and old weightstable female rats (270 g body weight) were used in two experiments. The IGF-I variant LR 3 IGF-I was continuously infused at 280 µg/day from 2 days before (early), concurrent with or 2 days after (delayed) commencement of a 6 day dexamethasone infusion (125 µg/kg per day).Both early and delayed treatment of young rats with LR 3 IGF-I significantly reduced the measured catabolic effects of dexamethasone. Early treatment was more effective than delayed treatment, with significantly higher nitrogen balance (90 12 vs 31 6 mg/day), carcass nitrogen gain (0·37 0·27 vs 1·13 0·10% per day) and protein fractional synthesis rates after 2 (10·4 0·5 vs 8·3 0·2% per day) and 6 days of dexamethasone (8·2 0·6 vs 7·0 0·3% per day). Similarly, fractional breakdown rates of carcass protein were maintained at significantly lower levels in rats given early treatment (6·23 0·24 vs 6·60 0·22% per day). In contrast, the old rats were less responsive to LR 3 IGF-I treatment and only early and concurrent treatment significantly reduced the catabolic response, partly because of higher food intake. Early treatment was superior to delayed treatment and led to significantly higher nitrogen balance ( 19 11 vs 83 7 mg/day) and carcass nitrogen fractional gain ( 1·19 0·40 vs 2·76 0·37% per day) as well as lower final rates of carcass protein fractional breakdown (3·55 0·15 vs 3·83 0·07% per day).These experiments show that early (prophylactic) treatment with IGF-I is superior to delayed treatment for reducing catabolism induced by dexamethasone. The results provide the basis for further research to determine if prophylactic IGF-I treatment is useful in other circumstances where catabolism can be anticipated, such as in elective major surgery.

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Physical Injury and Its Effects on Protein Metabolism

Cited by 38 publications

References 79 publications

Transcriptomic and proteomic analysis of liver and muscle alterations caused by surgical stress in rats

Transcriptomic and proteomic analysis of liver and muscle alterations caused by surgical stress in rats

Nutritional modulation of protein metabolism after gastrointestinal surgery

The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone

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