| 1. |
- Wernerman, Jan, et al.
(author)
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[Septic shock--a condition with great potential for improvement. Management and therapy].
- 2003
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 100:26-27, s. 2288-91
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Journal article (peer-reviewed)abstract
- There is a recent focus upon treatment of septic shock, related to the publication of a number of interesting studies during the last two years. These studies indicate that patient outcome can be improved, provided care is organized so as to optimize and expedite initial treatment of the patient in septic shock. In parallel, new drugs have been launched using rather aggressive marketing, which calls for recommendations and advice from professional experts who are independent of the pharmaceutical industry. This article reviews the studies that have engendered a new optimism in the treatment of septic shock. These "new" therapies are presented in a total context with a temporal perspective. It is suggested that emergency sepsis teams be instituted at hospitals.
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| 19. |
- Antonelli, Massimo, et al.
(author)
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Year in review in Intensive Care Medicine 2012. II : Pneumonia and infection, sepsis, coagulation, hemodynamics, cardiovascular and microcirculation, critical care organization, imaging, ethics and legal issues
- 2013
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In: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 39:3, s. 345-364
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Journal article (peer-reviewed)
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| 20. |
- Essén, Pia, et al.
(author)
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Laparoscopic cholecystectomy does not prevent the postoperative protein catabolic response in muscle
- 1995
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In: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 222:1, s. 36-42
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Journal article (peer-reviewed)abstract
- OBJECTIVE:The authors determined the effect of laparoscopic cholecystectomy on protein synthesis in skeletal muscle. In addition to a decrease in muscle protein synthesis, after open cholecystectomy, the authors previously demonstrated a decrease in insulin sensitivity. This study on patients undergoing laparoscopic and open surgery, therefore, included simultaneous measurements of protein synthesis and insulin sensitivity.SUMMARY BACKGROUND DATA:Laparoscopy has become a routine technique for several operations because of postoperative benefits that allow rapid recovery. However, its effect on postoperative protein catabolism has not been characterized. Conventional laparotomy induces a drop in muscle protein synthesis, whereas degradation is unaffected.METHODS:Patients were randomized to laparoscopic or open cholecystectomy, and the rate of protein synthesis in skeletal muscle was determined 24 hours postoperatively by the flooding technique using L-(2H5)phenylalanine, during a hyperinsulinemic normoglycemic clamp to assess insulin sensitivity.RESULTS:The protein synthesis rate decreased by 28% (1.77 +/- 0.11%/day vs. 1.26 +/- 0.08%/day, p < 0.01) in the laparoscopic group and by 20% (1.97 +/- 0.15%/day vs. 1.57 +/- 0.15%/day, p < 0.01) in the open cholecystectomy group. In contrast, the fall in insulin sensitivity after surgery was lower with laparoscopic (22 +/- 2%) compared with open surgery (49 +/- 5%).CONCLUSIONS:Laparoscopic cholecystectomy did not avoid a substantial decline in muscle protein synthesis, despite improved insulin sensitivity. The change in the two parameters occurred independently, indicating different mechanisms controlling insulin sensitivity and muscle protein synthesis.
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| 21. |
- Filip, Rafal S., et al.
(author)
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Alpha-ketoglutarate decreases serum levels of C-terminal cross-linking telopeptide of type I collagen (CTX) in postmenopausal women with osteopenia: Six-month study
- 2007
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In: International Journal for Vitamin and Nutrition Research. - : Hogrefe Publishing Group. - 0300-9831 .- 1664-2821. ; 77:2, s. 89-97
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Journal article (peer-reviewed)abstract
- Several studies have shown that alpha-ketoglutaric acid (AKG) increases serum levels of proline and has beneficial effects on skeletal development. We studied the effect of alpha-ketoglutaric (AKG) acid calcium salt (6 g AKG and 1,68 Ca/day) or calcium alone (1.68 Ca/day) on serum C-terminal cross-linked telopeptide of type I collagen (CTX) and osteocalcin (OC), as well as lumbar spine bone mineral density (BMD) in a randomized, parallel group, double-blind, 6-month study conducted on 76 postmenopausal women with osteopenia. The maximum decrease of the mean CTX level in the AKG-Ca group was observed after 24 weeks (37.0%, p = 0.006). The differences in CTX between study groups were statistically significant after 12 weeks and 24 weeks. The OC serum level was not affected by treatments. The BMD of the AKG-Ca group increased 1.6% from baseline; however, the difference between treatment groups was estimated as 0.9% (non-significant). This study suggests the potential usefulness of AKG-Ca in osteopenic postmenopausal women. AKG-Ca induced beneficial changes in serum CTX, which was consistent with preserving the bone mass in the lumbar spine; however, the long-term effect needs to be further investigated.
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| 22. |
- Fredriksson, Katarina, et al.
(author)
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Derangements in mitochondrial metabolism in intercostal and leg muscle of critically ill patients with sepsis-induced multiple organ failure
- 2006
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In: American Journal of Physiology. Endocrinology and Metabolism. - Bethesda, USA : American Physiological Society. - 0193-1849 .- 1522-1555. ; 291:5, s. E1044-50
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Journal article (peer-reviewed)abstract
- Critically ill patients treated for multiple organ failure often develop muscle dysfunction. Here we test the hypothesis that mitochondrial and energy metabolism are deranged in leg and intercostal muscle of critically ill patients with sepsis-induced multiple organ failure. Ten critically ill patients suffering from sepsis-induced multiple organ failure and requiring mechanical ventilation were included in the study. A group (n = 10) of metabolically healthy age- and sex-matched patients undergoing elective surgery were used as controls. Muscle biopsies were obtained from the vastus lateralis (leg) and intercostal muscle. The activities of citrate synthase and mitochondrial respiratory chain complexes I and IV and concentrations of ATP, creatine phosphate, and lactate were analyzed. Morphological evaluation of mitochondria was performed by electron microscopy. Activities of citrate synthase and complex I were 53 and 60% lower, respectively, in intercostal muscle of the patients but not in leg muscle compared with controls. The activity of complex IV was 30% lower in leg muscle but not in intercostal muscle. Concentrations of ATP and creatine phosphate were, respectively, 40 and 34% lower, and lactate concentrations were 43% higher in leg muscle but not in intercostal muscle. We conclude that both leg and intercostal muscle show a twofold decrease in mitochondrial content in intensive care unit patients with multiple organ failure, which is associated with lower concentrations of energy-rich phosphates and an increased anaerobic energy production in leg muscle but not in intercostal muscle.
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| 23. |
- Fredriksson, Katarina, et al.
(author)
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Dysregulation of Mitochondrial Dynamics and the Muscle Transcriptome in ICU Patients Suffering from Sepsis Induced Multiple Organ Failure
- 2008
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 3:11, s. e3686-
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Journal article (peer-reviewed)abstract
- Background: Septic patients treated in the intensive care unit (ICU) often develop multiple organ failure including persistent skeletal muscle dysfunction which results in the patient's protracted recovery process. We have demonstrated that muscle mitochondrial enzyme activities are impaired in septic ICU patients impairing cellular energy balance, which will interfere with muscle function and metabolism. Here we use detailed phenotyping and genomics to elucidate mechanisms leading to these impairments and the molecular consequences. Methodology/Principal Findings: Utilising biopsy material from seventeen patients and ten age-matched controls we demonstrate that neither mitochondrial in vivo protein synthesis nor expression of mitochondrial genes are compromised. Indeed, there was partial activation of the mitochondrial biogenesis pathway involving NRF2a/GABP and its target genes TFAM, TFB1M and TFB2M yet clearly this failed to maintain mitochondrial function. We therefore utilised transcript profiling and pathway analysis of ICU patient skeletal muscle to generate insight into the molecular defects driving loss of muscle function and metabolic homeostasis. Gene ontology analysis of Affymetrix analysis demonstrated substantial loss of muscle specific genes, a global oxidative stress response related to most probably cytokine signalling, altered insulin related signalling and a substantial overlap between patients and muscle wasting/inflammatory animal models. MicroRNA 21 processing appeared defective suggesting that post-transcriptional protein synthesis regulation is altered by disruption of tissue microRNA expression. Finally, we were able to demonstrate that the phenotype of skeletal muscle in ICU patients is not merely one of inactivity, it appears to be an actively remodelling tissue, influenced by several mediators, all of which may be open to manipulation with the aim to improve clinical outcome. Conclusions/Significance: This first combined protein and transcriptome based analysis of human skeletal muscle obtained from septic patients demonstrated that losses of mitochondria and muscle mass are accompanied by sustained protein synthesis (anabolic process) while dysregulation of transcription programmes appears to fail to compensate for increased damage and proteolysis. Our analysis identified both validated and novel clinically tractable targets to manipulate these failing processes and pursuit of these could lead to new potential treatments.
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| 24. |
- Hammarqvist, Folke, et al.
(author)
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Age-related changes of muscle and plasma amino acids in healthy children
- 2010
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In: Amino Acids. - : Springer Science and Business Media LLC. - 0939-4451 .- 1438-2199. ; 39:2, s. 359-366
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Journal article (peer-reviewed)abstract
- The aim of the study was to explore if changes in muscle and plasma amino acid concentrations developed during growth and differed from levels seen in adults. The gradient and concentrations of free amino acids in muscle and plasma were investigated in relation to age in metabolic healthy children. Plasma and specimens from the abdominal muscle were obtained during elective surgery. The children were grouped into three groups (group 1: < 1 year, n = 8; group 2: 1-4 years, n = 13 and group 3: 5-15 years, n = 15). A reference group of healthy adults (21-38 years, n = 22) was included in their comparisons and reflected specific differences between children and adults. In muscle the concentrations of 8 out of 19 amino acids analysed increased with age, namely taurine, aspartate, threonine, alanine, valine, isoleucine, leucine, histidine, as well as the total sums of branched chain amino acids (BCAA), basic amino acids (BAA) and total sum of amino acids (P < 0.05). In plasma the concentrations of threonine, glutamine, valine, cysteine, methionine, leucine, lysine, tryptophane, arginine, BCAA, BAA and the essential amino acids correlated with age (P < 0.05). These results indicate that there is an age dependency of the amino acid pattern in skeletal muscle and plasma during growth.
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| 25. |
- Helliksson, Fredrik, et al.
(author)
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The combined use of three widely available biochemical markers as predictor of organ failure in critically ill patients
- 2016
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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 76:6, s. 479-485
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Journal article (peer-reviewed)abstract
- Background: We hypothesized that lactate dehydrogenase, LDH/albumin ratio in combination with or without magnesium (Mg2+) could predict organ failure in critically ill adult patients. The aim of this study was to describe a new risk index for organ failure or mortality in critically ill patients based on a combination of these routinely available biochemical plasma biomarkers.Methods: Patients18 years admitted to the intensive care unit (ICU) were screened. Albumin and LDH were analyzed at the time of admission to ICU (n=347). Organ failure assessed with Sequential Organ Failure Assessment' (SOFA) score was used, and 30-day mortality was recorded. The predictive value of the test was calculated using the areas under the receiving operating characteristic (ROC) curve.Results: The LDH/albumin ratio was higher in patients who developed organ failure as compared to those who did not (p<0.001). The areas under the ROC curve were 0.77 both for prediction of multiple organ failure and for 30-day mortality. In a subgroup of patients (n=183) admitted to ICU from the emergency department, the predictive values were 0.86 and 0.80, respectively.Conclusion: The LDH/albumin ratio at ICU admission was associated with the development of multiple organ failure and 30-day mortality in this prospective study. The clinical value of this biomarker as a predictor of organ failure in critically ill patients is yet to be defined.
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| 26. |
- McNurlan, Margaret A., et al.
(author)
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Response of protein synthesis in human skeletal muscle to insulin : an investigation with L[2H5]phenylalanine
- 1994
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In: American Journal of Physiology. - : American Physiological Society. - 0002-9513 .- 2163-5773. ; 67:Part 1, s. E102-E108
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Journal article (peer-reviewed)abstract
- The role of insulin in the regulation of muscle protein synthesis in adult humans has been investigated with intravenous infusion of insulin at levels comparable with those observed after normal feeding. Glucose was also infused to maintain euglycemia. Muscle protein synthesis was measured in six healthy subjects before and during insulin and glucose infusion from the incorporation of L-[H-2(5)]phenylalanine into the protein of vastus lateralis sampled by percutaneous biopsy. L-[H-2(5)]phenylalanine was given as a single injection of a flooding amount (45 mg/kg). The relatively low levels of enrichment of phenylalanine in protein (0.005 atom%) were measured by modified gas chromatography-mass spectrometry and verified by comparison with incorporation of L-[2,6-H-3]phenylalanine. Similarity of enrichment in tissue-free and plasma pools (flooding) and linear incorporation over the period of measurement were also verified. The fractional rate of muscle protein synthesis in the group of postabsorptive subjects was 1.65 +/- 0.11% (SE)/day. The rate was unaltered by insulin and glucose infusion, 1.66 +/- 0.16%/day.
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| 27. |
- Nygren, Jonas, et al.
(author)
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Glucose flux is normalized by compensatory hyperinsulinaemia in growth hormone-induced insulin resistance in healthy subjects, while skeletal muscle protein synthesis remains unchanged.
- 2002
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In: Clinical Science. - London, United Kingdom : Portland Press. - 0143-5221 .- 1470-8736. ; 102:4, s. 457-64
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Journal article (peer-reviewed)abstract
- The aim of this present investigation was to study the relationship between the reduction in insulin sensitivity accompanying 5 days of treatment with growth hormone (GH; 0.05 mg.24 h(-1).kg(-1)) and intracellular substrate oxidation rates in six healthy subjects, while maintaining glucose flux by a constant glucose infusion and adjusting insulin infusion rates to achieve normoglycaemia (feedback clamp). Protein synthesis rates in skeletal muscle (flooding dose of L-[(2)H(5)]phenylalanine) were determined under these conditions. We also compared changes in insulin sensitivity after GH treatment with simultaneous changes in energy requirements, protein synthesis rates, nitrogen balance, 3-methylhistidine excretion in urine, body composition and the hormonal milieu. After GH treatment, 70% more insulin was required to maintain normoglycaemia (P<0.01). The ratio between glucose infusion rate and serum insulin levels decreased by 34% at the two levels of glucose infusion tested (P<0.05). Basal levels of C-peptide, insulin-like growth factor (IGF)-I and IGF-binding protein-3 increased almost 2-fold, while levels of glucose, insulin, glucagon, GH and IGF-binding protein-1 remained unchanged. Non-esterified fatty acid levels decreased (P<0.05). In addition, 24 h urinary nitrogen excretion decreased by 26% (P<0.01) after GH treatment, while skeletal muscle protein synthesis and 3-methylhistidine excretion in urine remained unchanged. Energy expenditure increased by 5% (P<0.05) after treatment, whereas fat and carbohydrate oxidation were unaltered. In conclusion, when glucose flux was normalized by compensatory hyperinsulinaemia under conditions of GH-induced insulin resistance, intracellular rates of oxidation of glucose and fat remained unchanged. The nitrogen retention accompanying GH treatment seems to be due largely to improved nitrogen balance in non-muscle tissue.
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| 28. |
- Parenmark, Fredric, 1974-
(author)
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Premature Discharge from Intensive Care with Special Reference to Night-Time Discharge and Capacity Transfers
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Objectives Intensive care is an expensive and limited resource, and when a demand supply mismatch between available beds and influx of patients occurs, one temporary measure is to discharge a patient to make room for the new admission. Sometimes the patient is discharged sooner from its original ICU than ideal; i.e., a so-called ‘premature discharge’. This could be either to a different ward within the same hospital if the patient is deemed well enough to cope with a lower level of care, or to another intensive care unit if critical care is still to be provided. Data from the Swedish intensive care register (SIR) showed that there was a high incidence and increased mortality of patients discharged at night. There were also differences in mortalities between patients that were transferred from one ICU to another. I have analysed the mortality associated with different types of ICU-to-ICU transfers and control groups and examined a national quality improvement project regarding discharges at night to see if mortality, incidence, or discharge culture could change. Methods All three studies are conducted with data from the Swedish intensive care register and vital status was ascertained by linking SIR to the Swedish population register. Study I consisted of two parts: mortality, and incidence of night-time discharge. The quality improvement project in Study I was analysed in a before and after approach with local improvement projects at different ICUs. In Studies II and III, transfers were grouped by the attending intensivist according to SIR guidelines into one of three defined categories: capacity transfer, clinical transfer, or repatriation. The groups were compared to each other in Study II, and capacity transfers were matched to a control group that remained in the ICU in Study III. Multilevel logistic regression was used, and all studies contained some statistics using individual ICUs as a random factor. Life sustaining treatment limitations were included in Studies II and III. Results In Study I, there was a decrease in night-time discharges during the study period. The incidence fell from 7.0% in 2006 to 4.9% in 2015. Alongside this, the mortality associated with night-time discharge was reduced, the odds ratio fell from 1.20 to 1.06 with a loss of significance. All this coincided in time with the national improvement project. Study II showed that 14.8% of all discharges from a Swedish ICU ended with transfer to another ICU, and that an increased mortality rate was associated with ICU-to-ICU transfers during periods of demand–supply mismatch. Capacity transfers were 15.8% of all transfers accounting for roughly 2.0% of ICU survivors. One in four capacity transferred patient died within 30 days of discharge, compared to one in seven for transfers due to clinical reasons. The third study showed that capacity transfer was associated with an average risk increase in 30-day mortality of 4.7%, and a 180-day mortality of 4.9% compared to non-transferred patients when analysed using a potential outcomes framework. Conclusion The studies concludes that patients experiencing a capacity transfer are exposed to increased mortality risk, both when compared to other types of inter hospital ICU-to-ICU transfers as well as when compared to patients that were not transferred. The increased risk appeared to be unrelated to patient characteristics and illness severity as well as many additional factors measured in the referring ICU. The studies also suggest that a suboptimal outcome after premature discharge at night can be changed and that a national project to adjust outcome and incidence can be undertaken with positive results.
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| 31. |
- Tonkonogi, Michail, et al.
(author)
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Reduced oxidative power but unchanged antioxidative capacity in skeletal muscle from aged humans.
- 2003
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In: Pflügers Archiv. - : Springer Science and Business Media LLC. - 0031-6768 .- 1432-2013. ; 446:2, s. 261-9
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Journal article (peer-reviewed)abstract
- The hypothesis that the aging process is associated with mitochondrial dysfunction and oxidative stress has been investigated in human skeletal muscle. Muscle biopsy samples were taken from seven old male subjects [OS; 75 (range 61-86) years] and eight young male subjects [YS; 25 (22-31) years]. Oxidative function was measured both in permeabilised muscle fibres and isolated mitochondria. Despite matching the degree of physical activity, OS had a lower training status than YS as judged from pulmonary maximal O(2) consumption ( Vdot;O(2)max, -36%) and handgrip strength (-20%). Both maximal respiration and creatine-stimulated respiration were reduced in muscle fibres from OS (-32 and -34%, respectively). In contrast, respiration in isolated mitochondria was similar in OS and YS. The discrepancy might be explained by a biased harvest of "healthy" mitochondria and/or disruption of structural components during the process of isolation. Cytochrome C oxidase was reduced (-40%, P<0.01), whereas UCP3 protein tended to be elevated in OS ( P=0.09). Generation of reactive oxygen species by isolated mitochondria and measures of antioxidative defence (muscle content of glutathione, glutathione redox status, antioxidative enzymes activity) were not significantly different between OS and YS. It is concluded that aging is associated with mitochondrial dysfunction, which appears to be unrelated to reduced physical activity. The hypothesis of increased oxidative stress in aged muscle could not be confirmed in this study.
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| 32. |
- Westman, Bo, et al.
(author)
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Effects on skeletal muscle glutathione status of ischemia and reperfusion following abdominal aortic aneurysm surgery.
- 2006
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In: Annals of Vascular Surgery. - : Elsevier BV. - 0890-5096 .- 1615-5947. ; 20:1, s. 99-105
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Journal article (peer-reviewed)abstract
- Glutathione (GSH) is an important endogenous scavenger against reactive oxygen species. Elective abdominal surgery without ischemia and reperfusion leads to decreased muscle GSH concentrations 4-72 hr postoperatively without altering GSH redox status. In the present study, we investigated to what extent muscle GSH status was affected during and following elective abdominal aortic aneurysm repair. From patients (n = 10) undergoing abdominal aortic repair, thigh muscle specimens were taken preoperatively, at maximal ischemia, and at 10 min and 4, 24, and 48 hr of reperfusion. Specimens were analyzed for GSH, amino acids, and energy-rich compounds. At maximal ischemia, phosphocreatine decreased by 37% (p < 0.05) and lactate and creatine increased by 274% and 57% (p < 0.001 and 0.05), respectively, indicating ischemia during the clamping of aorta. Adenosine triphosphate, on the other hand, remained unaltered during the entire study period. Total GSH (tGSH) decreased by 46% at 24 hr and by 43% at 48 hr of reperfusion (p < 0.001), while reduced GSH decreased by 48% at 24 hr and by 44% at 48 hr (p < 0.001). The redox status (GSH/tGSH) of GSH and oxidized GSH remained unaltered. Among the constituent amino acids of GSH, glycine and cysteine remained unaltered while glutamine and glutamate decreased by 55% and 55%, respectively (p < 0.001). Abdominal aortic aneurysm repair induces metabolic alterations characteristic for ischemia. The antioxidative capacity in terms of muscle levels of GSH was decreased. However, the oxidative stress during reperfusion did not change GSH status more than what has been reported following abdominal surgery without ischemia and reperfusion. The results indicate that the oxidative stress elicited by elective abdominal aortic aneurysm repair is outbalanced by a compensated GSH metabolism not giving rise to an increased amount of oxidized GSH or an altered GSH redox status.
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