Summary of Study ST001868
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001179. The data can be accessed directly via it's Project DOI: 10.21228/M89M5S This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST001868 |
| Study Title | Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor (part II) |
| Study Type | untargeted NMR analysis-noesy |
| Study Summary | Previous studies in our laboratory have suggested that the increase in stillbirth in pregnancies complicated by chronic maternal stress or hypercortisolemia is associated with cardiac dysfunction in late stages of labor and delivery. Transcriptomics analysis of the overly represented differentially expressed genes in the fetal heart of hypercortisolemic ewes indicated involvement of mitochondrial function. Sodium dichloroacetate (DCA) has been used to improve mitochondrial function in several disease states. We hypothesized that administration of DCA to laboring ewes would improve both cardiac mitochondrial activity and cardiac function in their fetuses. Four groups of ewes and their fetuses were studied: control, cortisol-infused (1 g/kg/d from 115 to term; CORT), DCA-treated (over 24h) or DCA+CORT-treated; oxytocin was delivered starting 48h before the DCA treatment. DCA significantly decreased cardiac lactate, alanine and glucose/glucose-6-phosphate and increased acylcarnitine/isobutyryl-carnitine. DCA increased mitochondrial activity, increasing oxidative phosphorylation (PCI, PCI+II)) per tissue weight or per unit of citrate synthase. DCA also decreased the duration of the QRS, attenuating the prolongation of the QRS observed in CORT fetuses. The effect to reduce QRS duration with DCA treatment correlated with increased glycerophosphocholine and serine and decreased phophocholine after DCA treatment. There were negative correlations of acylcarnitine/isobutyryl-carnitine to both HR and MAP. These results suggest that improvements in mitochondrial respiration with DCA produced changes in the cardiac lipid metabolism that favor improved conduction in the heart. DCA may therefore be an effective treatment of fetal cardiac metabolic disturbances in labor that can contribute to impairments of fetal cardiac conduction. |
| Institute | University of Georgia |
| Department | Biochemistry and Molecular Biology and Complex Carbohydrate Research Center, Department of Pharmacodynamics (University of Florida), Department of Physiology and Functional Genomics (University of Florida) |
| Laboratory | Edison Lab, Keller-Wood Lab, and Wood Lab |
| Last Name | Zhang |
| First Name | Sicong |
| Address | 315 Riverbend Road, Complex Carbohydrate Research Center |
| sz91614@uga.edu | |
| Phone | 7067151662 |
| Submit Date | 2021-07-01 |
| Num Groups | 4 |
| Total Subjects | 29 |
| Publications | Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor DOI:https://doi.org/10.1152/ajpregu.00185.2021 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | fid |
| Analysis Type Detail | NMR |
| Release Date | 2021-07-22 |
| Release Version | 1 |
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Project:
| Project ID: | PR001179 |
| Project DOI: | doi: 10.21228/M89M5S |
| Project Title: | Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor |
| Project Type: | untargeted NMR analysis |
| Project Summary: | Previous studies in our laboratory have suggested that the increase in stillbirth in pregnancies complicated by chronic maternal stress or hypercortisolemia is associated with cardiac dysfunction in late stages of labor and delivery. Transcriptomics analysis of the overly represented differentially expressed genes in the fetal heart of hypercortisolemic ewes indicated involvement of mitochondrial function. Sodium dichloroacetate (DCA) has been used to improve mitochondrial function in several disease states. We hypothesized that administration of DCA to laboring ewes would improve both cardiac mitochondrial activity and cardiac function in their fetuses. Four groups of ewes and their fetuses were studied: control, cortisol-infused (1 g/kg/d from 115 to term; CORT), DCA-treated (over 24h) or DCA+CORT-treated; oxytocin was delivered starting 48h before the DCA treatment. DCA significantly decreased cardiac lactate, alanine and glucose/glucose-6-phosphate and increased acylcarnitine/isobutyryl-carnitine. DCA increased mitochondrial activity, increasing oxidative phosphorylation (PCI, PCI+II)) per tissue weight or per unit of citrate synthase. DCA also decreased the duration of the QRS, attenuating the prolongation of the QRS observed in CORT fetuses. The effect to reduce QRS duration with DCA treatment correlated with increased glycerophosphocholine and serine and decreased phophocholine after DCA treatment. There were negative correlations of acylcarnitine/isobutyryl-carnitine to both HR and MAP. These results suggest that improvements in mitochondrial respiration with DCA produced changes in the cardiac lipid metabolism that favor improved conduction in the heart. DCA may therefore be an effective treatment of fetal cardiac metabolic disturbances in labor that can contribute to impairments of fetal cardiac conduction. |
| Institute: | University of Georgia |
| Department: | Biochemistry and Molecular Biology and Complex Carbohydrate Research Center, Department of Pharmacodynamics (University of Florida), Department of Physiology and Functional Genomics (University of Florida) |
| Laboratory: | Edison Lab, Keller-Wood Lab, and Wood Lab |
| Last Name: | Edison |
| First Name: | Arthur |
| Address: | 315 Riverbend Road, Complex Carbohydrate Research Center, ATHENS, GA, 30605, USA |
| Email: | aedison@uga.edu |
| Phone: | NA |
| Publications: | Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor DOI:https://doi.org/10.1152/ajpregu.00185.2021 |
| Contributors: | Serene Joseph, Mengchen Li, Sicong Zhang, Lloyd Horne, Peter. W. Stacpoole, Stephanie E. Wohlgemuth, Arthur S. Edison, Charles Wood, Maureen Keller-Wood |
