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.
| 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 |
| 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 |
Select appropriate tab below to view additional metadata details:
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 |
Subject:
| Subject ID: | SU001944 |
| Subject Type: | Mammal |
| Subject Species: | Ovis aries |
| Taxonomy ID: | 9940 |
| Animal Inclusion Criteria: | Pregnant |
Factors:
Subject type: Mammal; Subject species: Ovis aries (Factor headings shown in green)
| mb_sample_id | local_sample_id | Cortisol treatment | DCA treatment |
|---|---|---|---|
| SA174508 | 1656_R | Control | Control |
| SA174509 | 1532_R | Control | Control |
| SA174510 | 1324_L | Control | Control |
| SA174511 | 1427_S | Control | Control |
| SA174512 | 1611_S | Control | Control |
| SA174513 | 1532_L | Control | Control |
| SA174514 | 1775_S | Control | Control |
| SA174515 | 1775_R | Control | Control |
| SA174516 | 1611_R | Control | Control |
| SA174517 | 1254_R | Control | Control |
| SA174518 | 1775B_R | Control | Control |
| SA174519 | 1324_R | Control | Control |
| SA174520 | 1254_S | Control | Control |
| SA174521 | 1427_R | Control | Control |
| SA174522 | 1656_L | Control | Control |
| SA174523 | 1775B_L | Control | Control |
| SA174524 | 1532_S | Control | Control |
| SA174525 | 1611_L | Control | Control |
| SA174526 | 1656_S | Control | Control |
| SA174527 | 1427_L | Control | Control |
| SA174528 | 1775_L | Control | Control |
| SA174529 | 1324_S | Control | Control |
| SA174530 | 1254_L | Control | Control |
| SA174531 | 1775B_S | Control | Control |
| SA174532 | 1269_S | Control | DCA-treated (over 24h) |
| SA174533 | 1401_R | Control | DCA-treated (over 24h) |
| SA174534 | 1401_S | Control | DCA-treated (over 24h) |
| SA174535 | 1356_R | Control | DCA-treated (over 24h) |
| SA174536 | 3019_R | Control | DCA-treated (over 24h) |
| SA174537 | 1269_R | Control | DCA-treated (over 24h) |
| SA174538 | 1682_L | Control | DCA-treated (over 24h) |
| SA174539 | 3022_S | Control | DCA-treated (over 24h) |
| SA174540 | 1277_S | Control | DCA-treated (over 24h) |
| SA174541 | 1603_S | Control | DCA-treated (over 24h) |
| SA174542 | 1356_S | Control | DCA-treated (over 24h) |
| SA174543 | 1719_S | Control | DCA-treated (over 24h) |
| SA174544 | 1277_R | Control | DCA-treated (over 24h) |
| SA174545 | 3019_S | Control | DCA-treated (over 24h) |
| SA174546 | 1603_R | Control | DCA-treated (over 24h) |
| SA174547 | 1682_S | Control | DCA-treated (over 24h) |
| SA174548 | 3022_R | Control | DCA-treated (over 24h) |
| SA174549 | 3022_L | Control | DCA-treated (over 24h) |
| SA174550 | 1603_L | Control | DCA-treated (over 24h) |
| SA174551 | 1277_L | Control | DCA-treated (over 24h) |
| SA174552 | 1356_L | Control | DCA-treated (over 24h) |
| SA174553 | 1719_L | Control | DCA-treated (over 24h) |
| SA174554 | 1401_L | Control | DCA-treated (over 24h) |
| SA174555 | 1719_R | Control | DCA-treated (over 24h) |
| SA174556 | 1269_L | Control | DCA-treated (over 24h) |
| SA174557 | 3019_L | Control | DCA-treated (over 24h) |
| SA174558 | 1682_R | Control | DCA-treated (over 24h) |
| SA174559 | 1261_S | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174560 | 1329_S | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174561 | 1397_L | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174562 | 1727_S | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174563 | 1397_S | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174564 | 1448_S | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174565 | 1448_L | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174566 | 1727_L | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174567 | 1565_S | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174568 | 1428_S | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174569 | 1397_R | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174570 | 1261_R | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174571 | 1329_L | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174572 | 1428_L | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174573 | 1261_L | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174574 | 1329_R | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174575 | 1565_L | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174576 | 1428_R | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174577 | 1448_R | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174578 | 1727_R | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174579 | 1565_R | Cortisol-infused (1 g/kg/d from 115 to term) | Control |
| SA174580 | 1212_L | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174581 | 1445_S | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174582 | 1668_L | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174583 | 1642_S | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174584 | 1668_S | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174585 | 1642_R | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174586 | 1445_R | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174587 | 1668_R | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174588 | 1606_R | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174589 | 1642_L | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174590 | 1445_L | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174591 | 1212_S | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174592 | 1606_L | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174593 | 1212_R | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| SA174594 | 1606_S | Cortisol-infused (1 g/kg/d from 115 to term) | DCA-treated (over 24h) |
| Showing results 1 to 87 of 87 |
Collection:
| Collection ID: | CO001937 |
| Collection Summary: | Heart tissue was collected from the right ventricle, left ventricle, and intraventricular septum and immediately frozen in liquid nitrogen. |
| Sample Type: | Heart |
| Storage Conditions: | -80℃ |
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. |
Sample Preparation:
| Sampleprep ID: | SP001950 |
| Sampleprep Summary: | Heart tissues were cut to ~ 30 mg and weighted. Each tissue was added to 30 µl of D2O with 10/3 mM sodium trimethylsilylpropane-sulfonate (DSS) and transferred to a 4-mm zirconium dioxide rotor with Kel-F cap and PTFE spacer provided by Bruker Biospin. Samples were kept on dry ice during sample preparation. |
Analysis:
| Analysis ID: | AN003029 |
| Laboratory Name: | Edison Lab |
| Analysis Type: | NMR |
| Software Version: | Topspin 4.0.6 |
NMR:
| NMR ID: | NM000208 |
| Analysis ID: | AN003029 |
| Instrument Name: | Bruker NEO 600MHz |
| Instrument Type: | FT-NMR |
| NMR Experiment Type: | 1D-1H |
| Field Frequency Lock: | D2O |
| Spectrometer Frequency: | 600 MHz |
| NMR Probe: | 4mm CMP_HRMAS |
| NMR Solvent: | D2O |
| NMR Tube Size: | 50 ul |
| Shimming Method: | manual |
| Pulse Sequence: | cpmgpr1d |
| Water Suppression: | presat |
| Receiver Gain: | 101 |
| Chemical Shift Ref Cpd: | DSS |
| Temperature: | 10 |
| Number Of Scans: | 128 |
| Dummy Scans: | 8 |
| Acquisition Time: | 0.69 s |
| Spectral Width: | 19.8393 |
| Num Data Points Acquired: | 16384 |
| Line Broadening: | 1.8 |
| Baseline Correction Method: | ABSG |
| NMR Results File: | CPMG_binned_data.txt UNITS:(relative) |
