Dataset Information

Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival.

ABSTRACT: BACKGROUND:Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular and immune function. NO is generated by nitric oxide synthases (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NOS. Increased inhibitor blood concentrations lead to reduce NO bioavailability. The aim of this study was to determine whether plasma concentrations of SDMA and ADMA are markers for sepsis survival. METHOD:This prospective, single center study involved 120 ICU patients with sepsis. Plasma SDMA and ADMA were measured on admission (day 1), day 3 and day 7 by mass spectrometry together with other laboratory markers. The sequential organ failure assessment (SOFA) score was used to evaluate sepsis severity. Survival was documented until day 28. Groups were compared using the Mann-Whitney U test, chi-squared test or non-parametric analysis of variance (ANOVA). Mortality was assessed using Kaplan-Meier curves and compared using the log-rank test. Specific risk groups were identified using a decision tree algorithm. RESULTS:Median plasma SDMA and ADMA levels were significantly higher in non-survivors than in survivors of sepsis: SDMA 1.14 vs. 0.82 ?mol/L (P?=?0.002) and ADMA 0.93 vs. 0.73 ?mol/L (P?=?0.016). ANOVA showed that increased plasma SDMA and ADMA concentrations were significantly associated with SOFA scores. The 28-day mortality was compared by chi-square test: for SDMA the mortality was 12% in the lower, 25% in the intermediate and 43% in the 75th percentile (P?=?0.018); for ADMA the mortality was 18-20% in the lower and intermediate but 48% in the 75th percentile (P?=?0.006). The highest mortality (61%) was found in patients with plasma SDMA >?1.34 together with ADMA levels >?0.97 ?mol/L. CONCLUSIONS:Increased plasma concentrations of SDMA and ADMA are associated with sepsis severity. Therefore, our findings suggest reduced NO bioavailability in non-survivors of sepsis. One may use individual SDMA and ADMA levels to identify patients at risk. In view of the pathophysiological role of NO we conclude that the vascular system and immune response are most severely affected when SDMA and ADMA levels are high.

SUBMITTER: Winkler MS

PROVIDER: S-EPMC6145330 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival.

Winkler Martin Sebastian MS Nierhaus Axel A Rösler Gilbert G Lezius Susanne S Harlandt Olaf O Schwedhelm Edzard E Böger Rainer H RH Kluge Stefan S

Critical care (London, England) 20180919 1

<h4>Background</h4>Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular and immune function. NO is generated by nitric oxide synthases (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NOS. Increased inhibitor blood concentrations lead to reduce NO bioavailability. The aim of this study was to determine whether plasma concentrations of SDMA an ...[more]

PMID: 30231905

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Project description:BackgroundSynergy modules have been used to describe activation of lower limb muscles during locomotion and hence to understand how the system controls movement. Walking and running have been shown shared synergy patterns suggesting common motor control of both symmetrical gaits. Unilateral skipping, an equivalent gait to the quadrupedal gallop in humans, has been defined as the third locomotion paradigm but the use by humans is limited due to its high metabolic cost. Synergies in skipping have been little investigated. In particular, to the best of our knowledge, the joint study of both trailing and leading limbs has never been addressed before.Research questionHow are organized muscle activation patterns in unilateral skipping? Are they organized in the same way that in symmetrical gaits? If yes, which are the muscle activation patterns in skipping that make it a different gait to walking or running? In the present research, we investigate if there are shared control strategies for all gaits in locomotion. Addressing these questions in terms of muscle synergies could suggest possible determinants of the scarce use of unilateral skipping in humans.MethodsElectromyographic data of fourteen bilateral muscles were collected from volunteers while performing walking, running and unilateral skipping on a treadmill. Also, spatiotemporal gait parameters were computed from 3D kinematics. The modular composition and activation timing extracted by non-negative matrix factorization were analyzed to detect similarities and differences among symmetrical gaits and unilateral skipping.ResultsSynergy modules showed high similarity throughout the different gaits and between trailing and leading limbs during unilateral skipping. The synergy associated with the propulsion force operated by calf muscles was anticipated in bouncing gaits. Temporal features of synergies in the leading leg were very similar to those observed for running. The different role of trailing and leading legs in unilateral skipping was reflected by the different timing in two modules. Activation for weight acceptance was anticipated and extended in the trailing leg, preparing the body for landing impact after the flight phase. A different behaviour was detected in the leading leg, which only deals with a pendular weight transference.SignificanceThe evidence gathered in this work supports the hypothesis of shared modules among symmetrical and asymmetrical gaits, suggesting a common motor control despite of the infrequent use of unilateral skipping in humans. Unilateral skipping results from phase-shifted activation of similar muscular groups used in symmetrical gaits, without the need for new muscular groups. The high and anticipated muscle activation in the trailing leg for landing could be the key distinctive event of unilateral skipping.

Dataset Information

Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival.

Publications

Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival.

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