Summary of Study ST001867

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.

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Study ID	ST001867
Study Title	Sodium dichloroacetate stimulates cardiac mitochondrial metabolism and improves cardiac conduction in the ovine fetus during labor (part I)
Study Type	untargeted NMR analysis-cpmg
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
Email	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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Treatment:

Treatment ID:	TR001956
Treatment Summary:	Animals in the CORT and CORT+DCA groups were implanted with pellets of cortisol hemisuccinate (Innovative Research, Sarasota, FL) or infused with cortisol hemisuccinate (Solu-Cortef, Pfizer, Inc) using an ambulatory pump (3D Micro Infusion Pump; Strategic Applications Inc.; Lake Villa, IL) to provide dosing of cortisol at 1mg/kg/day beginning on day 115-116 of gestation until the end of the experiment when the animals were sacrificed. This dose of cortisol increased maternal cortisol concentrations to approximately 1.5-fold, mimicking the rise in cortisol in moderate stress. To produce a regular pattern of labor, ewes were infused with oxytocin (Aspen Veterinary Resources) beginning at day 138-140 of gestation; oxytocin was infused over 5 minutes every 30 minutes (820 µU/kg/min iv;) using an infusion pump controlled by a timed controller ChronTrol Corp, Inc). DCA infusion was started 48 hours after the start of oxytocin. DCA was administered as an intravenous bolus of 25 mg/kg over 3 minutes, followed by an infusion of 12.5 mg DCA/kg/hour for 8 hours, and an infusion of 6.25 mg DCA/kg/h for the next 8 hours. These doses are similar to those that significantly decrease circulating lactate concentrations in humans. The timed infusions of oxytocin continued for 72 hours, and the study was terminated after 24 hours of DCA and/or 72 hours of oxytocin infusion, unless ewes were in the process of delivery or birth occurred.

Treatment ID:

TR001956

Treatment Summary:

Animals in the CORT and CORT+DCA groups were implanted with pellets of cortisol hemisuccinate (Innovative Research, Sarasota, FL) or infused with cortisol hemisuccinate (Solu-Cortef, Pfizer, Inc) using an ambulatory pump (3D Micro Infusion Pump; Strategic Applications Inc.; Lake Villa, IL) to provide dosing of cortisol at 1mg/kg/day beginning on day 115-116 of gestation until the end of the experiment when the animals were sacrificed. This dose of cortisol increased maternal cortisol concentrations to approximately 1.5-fold, mimicking the rise in cortisol in moderate stress. To produce a regular pattern of labor, ewes were infused with oxytocin (Aspen Veterinary Resources) beginning at day 138-140 of gestation; oxytocin was infused over 5 minutes every 30 minutes (820 µU/kg/min iv;) using an infusion pump controlled by a timed controller ChronTrol Corp, Inc). DCA infusion was started 48 hours after the start of oxytocin. DCA was administered as an intravenous bolus of 25 mg/kg over 3 minutes, followed by an infusion of 12.5 mg DCA/kg/hour for 8 hours, and an infusion of 6.25 mg DCA/kg/h for the next 8 hours. These doses are similar to those that significantly decrease circulating lactate concentrations in humans. The timed infusions of oxytocin continued for 72 hours, and the study was terminated after 24 hours of DCA and/or 72 hours of oxytocin infusion, unless ewes were in the process of delivery or birth occurred.