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Effects of l-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol

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Abstract

Not much is known about effects of gestational alcohol exposure on maternal and fetal cardiovascular adaptations. This study determined whether maternal binge alcohol exposure and l-glutamine supplementation could affect maternal-fetal hemodynamics and fetal regional brain blood flow during the brain growth spurt period. Pregnant sheep were randomly assigned to one of four groups: saline control, alcohol (1.75–2.5 g/kg body weight), glutamine (100 mg/kg body weight) or alcohol + glutamine. A chronic weekend binge drinking paradigm between gestational days (GD) 99 and 115 was utilized. Fetuses were surgically instrumented on GD 117 ± 1 and studied on GD 120 ± 1. Binge alcohol exposure caused maternal acidemia, hypercapnea, and hypoxemia. Fetuses were acidemic and hypercapnic, but not hypoxemic. Alcohol exposure increased fetal mean arterial pressure, whereas fetal heart rate was unaltered. Alcohol exposure resulted in ~40 % reduction in maternal uterine artery blood flow. Labeled microsphere analyses showed that alcohol induced >2-fold increases in fetal whole brain blood flow. The elevation in fetal brain blood flow was region-specific, particularly affecting the developing cerebellum, brain stem, and olfactory bulb. Maternal l-glutamine supplementation attenuated alcohol-induced maternal hypercapnea, fetal acidemia and increases in fetal brain blood flow. l-Glutamine supplementation did not affect uterine blood flow. Collectively, alcohol exposure alters maternal and fetal acid–base balance, decreases uterine blood flow, and alters fetal regional brain blood flow. Importantly, l-glutamine supplementation mitigates alcohol-induced acid–base imbalances and alterations in fetal regional brain blood flow. Further studies are warranted to elucidate mechanisms responsible for alcohol-induced programming of maternal uterine artery and fetal circulation adaptations in pregnancy.

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Acknowledgments

We would like to acknowledge the important role of the late Dr. Timothy Cudd in starting this study and making significant contributions. We would like to thank Raine Lunde, Brittney Kramer, Tracie Hohman, Kelsey Nation, Sarah Baker, Zoe Browning, Dillon Johnson, Lance Wheeler, Colt Sharpton, and Sudath Dahanayaka for their assistance in this study. This research was supported by NIAAA grant AA010940 (SW and GW) and AA18166-2 (SW), AA19446 (JR).

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The authors have no conflicts of interest to disclose.

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Authors and Affiliations

  1. Department of Veterinary Physiology and Pharmacology and Michael E. DeBakey Institute, College of Veterinary Medicine and Biomedical Sciences, 4466 Texas A&M University, College Station, TX, 77843-4466, USA

    Onkar B. Sawant & Shannon E. Washburn

  2. Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, 77555, USA

    Jayanth Ramadoss & Gary D. Hankins

  3. Department of Animal Science, Texas A&M University, College Station, TX, 77843, USA

    Guoyao Wu

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  1. Onkar B. Sawant
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  2. Jayanth Ramadoss
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  3. Gary D. Hankins
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  4. Guoyao Wu
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  5. Shannon E. Washburn
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Correspondence to Shannon E. Washburn.

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Sawant, O.B., Ramadoss, J., Hankins, G.D. et al. Effects of l-glutamine supplementation on maternal and fetal hemodynamics in gestating ewes exposed to alcohol. Amino Acids 46, 1981–1996 (2014). https://doi.org/10.1007/s00726-014-1751-x

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  • DOI: https://doi.org/10.1007/s00726-014-1751-x

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