Relationship between Isoprostane Concentrations, Metabolic Acidosis, and Morbid Neonatal Outcome

Abstract

arginine and ADMA and SDMA, respectively. The addition of l-arginine, ADMA, or SDMA did not influence the measurement of the other analytes. We also determined within-and between-run imprecision (CVs; n ϭ 10). The within-run CVs were 3.3% for l-arginine, 2.6% for ADMA, and 2.5% for SDMA. Between-run CVs were 4.7% for l-arginine, 4.1% for ADMA, and 3.9% for SDMA We also measured ADMA in plasma samples from healthy human volunteers (n ϭ 22) by this LC-MS/MS method. Shown in Fig. 1 is a typical chromatogram of a human plasma sample. Samples were aliquoted (50 L) and frozen at Ϫ20°C before analysis. The mean (SD) concentrations of l-arginine, ADMA, and SDMA were 65.6 (23.4), 0.55 (0.14), and 0.69 (0.23) mol/L, respectively. The mean (SD) molar ratio of l-arginine to ADMA was 132 (55).Our LC-MS/MS-based method allows for the simultaneous determination of ADMA, SDMA, and l-arginine and has been validated for the measurement of these 3 analytes in human plasma. Values obtained for l-arginine, ADMA, and SDMA in human plasma are within previously reported ranges (11)(12)(13)16 ). Major advantages over previous reported methods for the measurement of ADMA include a minimized sample volume and reduction in laboratory work. In particular, in comparison with other LC-MS-based methods (13,14,16,17 ), sample run time has been reduced to 4 min including reequilibration. Chromatographic separation required only slightly more than 2 min. This considerable reduction in analysis time was achieved by use of the specific fragmentation patterns of the ester derivatives of ADMA and SDMA. Identical MS spectra were obtained from the ester derivatives of ADMA and SDMA, but the major fragments in the daughter ion spectra for ADMA and SDMA were at m/z 214 and m/z 228, respectively. These ions were specific for ADMA and SDMA: they were absent in the corresponding spectra of SDMA and ADMA, respectively. In contrast to previous reports, the proposed method allows, for the first time, spectrometric instead of chromatographic separation of these methylated arginines (see the Data Supplement that accompanies the online version of this Technical Brief at http://www.clinchem.org/content/ vol51/issue7/). When a fetus is subjected to a massive perinatal hypoxicischemic insult, it may suffer sufficient damage to cause intrauterine death and stillbirth (1)(2)(3)(4)(5). In less severe,

Preliminary case control study to establish the correlation between novel peroxidation biomarkers in cord serum and the severity of hypoxic ischemic encephalopathy

“…Actually, increased brain levels of 8-epi-PGF2a were found in asphyctic newborn rats 2 h after global perinatal asphyxia, and this biomarker could be predictive of delayed behavioral disturbances [22]. These biomarkers have several advantages, such as establishing a quantitative result and diagnosis to clinically undefined samples, and being potential long-term neurological damage biomarkers [14,22]. This fact can be explained by the molecular damage occurred under hypoxic episode depending on its intensity, duration, previous metabolic state, gestational age, and the degree of development of the antioxidant system, altogether these factors can induce a different response to a hypoxic episode.…”

“…The role of oxidative stress biomarkers has been reviewed [14]. In the experimental setting metabolomic studies performed in animal models of hypoxia reoxygenation have shown that oxidative stress associated metabolites strongly correlate with brain injury.…”

Molecular Mechanisms Regulating the Vascular Prostacyclin Pathways and Their Adaptation during Pregnancy and in the Newborn

“…Likewise, vascular disorders of the newborn involve disturbed not only PGI 2 , TXA 2 , and PGE 2 metabolism but also changes in other eicosanoids (Ostrea et al, 2006). Isoprostanes have been associated with increased morbidity of neonatal PPHN (Gong et al, 2010), ROP (Hardy et al, 2000), and HIE (Rogers et al, 2005). On the other hand, in addition to the cytoprotective role of PGI 2 in later stages of ischemic injury associated with HIE, PGD 2 acting through DP1 receptors may protect the neonatal brain against EC degeneration (Taniguchi et al, 2007).…”

Cord blood 8-isoprostane in the preterm infant

“…25 Similarly, most reports of cord blood lipid peroxidation in fetal distress have been in term infants. 26-29 These studies also show marked variability that appears to be influenced by obstetrical intervention and mode of delivery. 30-32 Consistent with these findings in our preterm population, covariates of medical intervention (e.g., artificial ROM, tocolysis, c-section delivery) all had odds ratios <1.0 with elevated 8-IP, suggesting a protective effect.…”