Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function
Ryan Atkins, Dumitru Constantin-Teodosiu, Krishna K Varadhan, Despina Constantin, Dileep N Lobo, Paul L Greenhaff, Ryan Atkins, Dumitru Constantin-Teodosiu, Krishna K Varadhan, Despina Constantin, Dileep N Lobo, Paul L Greenhaff
Abstract
Background & aims: This post hoc study aimed to determine whether major elective abdominal surgery had any acute impact on mitochondrial pyruvate dehydrogenase complex (PDC) activity and maximal mitochondrial ATP production rates (MAPR) in a large muscle group (vastus lateralis -VL) distant to the site of surgical trauma.
Methods: Fifteen patients undergoing major elective open abdominal surgery were studied. Muscle biopsies were obtained after the induction of anesthesia from the VL immediately before and after surgery for the determination of PDC and maximal MAPR (utilizing a variety of energy substrates).
Results: Muscle PDC activity was reduced by >50% at the end of surgery compared with pre-surgery (p < 0.05). Muscle MAPR were comprehensively suppressed by surgery for the substrate combinations: glutamate + succinate; glutamate + malate; palmitoylcarnitine + malate; and pyruvate + malate (all p < 0.05), and could not be explained by a lower mitochondrial yield.
Conclusions: PDC activity and mitochondrial ATP production capacity were acutely impaired in muscle distant to the site of surgical trauma. In keeping with the limited data available, we surmise these events resulted from the general anesthesia procedures employed and the surgery related trauma. These findings further the understanding of the acute dysregulation of mitochondrial function in muscle distant to the site of major surgical trauma in patients, and point to the combination of general anesthesia and trauma related inflammation as being drivers of muscle metabolic insult that warrants further investigation.
Clinical trial registration: Registered at (NCT01134809).
Keywords: Abdominal surgery; Metabolic response; Muscle inflammatory responses; Muscle mitochondrial activity; Pyruvate dehydrogenase complex.
Conflict of interest statement
Conflict of interest None of the authors has a direct conflict of interest to report. DN Lobo has received an unrestricted research grant for unrelated work from B. Braun in the last 3 years. He has also received speakers' honoraria from B. Braun, Fresenius Kabi, Shire and Baxter Healthcare for unrelated work in the last 3 years.
Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Figures
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Fig. 2
Maximal mitochondrial ATP production rates…
Fig. 2
Maximal mitochondrial ATP production rates in vastus lateralis muscle pre and post major…
- Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery.Varadhan KK, Constantin-Teodosiu D, Constantin D, Greenhaff PL, Lobo DN. Varadhan KK, et al. Clin Nutr. 2018 Dec;37(6 Pt A):2178-2185. doi: 10.1016/j.clnu.2017.10.020. Epub 2017 Nov 2. Clin Nutr. 2018. PMID: 29129636 Free PMC article.
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- Thorell A., Nygren J., Ljungqvist O. Insulin resistance: a marker of surgical stress. Curr Opin Clin Nutr Metab Care. 1999;2:69–78. - PubMed
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- Hagve M., Gjessing P.F., Fuskevåg O.M., Larsen T.S., Irtun Ø. Skeletal muscle mitochondria exhibit decreased pyruvate oxidation capacity and increased ROS emission during surgery-induced acute insulin resistance. Am J Physiol Endocrinol Metab. 2015;308:E613–E620. - PubMed
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- Gjessing P.F., Constantin-Teodosiu D., Hagve M., Lobo D.N., Revhaug A., Irtun O. Preoperative carbohydrate supplementation attenuates post-surgery insulin resistance via reduced inflammatory inhibition of the insulin-mediated restraint on muscle pyruvate dehydrogenase kinase 4 expression. Clin Nutr. 2015;34:1177–1183. - PubMed
- Observational Study
- Research Support, Non-U.S. Gov't
- Abdomen / surgery*
- Adenosine Triphosphate / metabolism*
- Biopsy
- Female
- Humans
- Lower Extremity / physiopathology
- Male
- Middle Aged
- Mitochondria, Muscle / metabolism*
- Muscle, Skeletal / cytology
- Muscle, Skeletal / metabolism*
- Postoperative Period
- Pyruvate Dehydrogenase Complex / metabolism*
- Pyruvate Dehydrogenase Complex
- Adenosine Triphosphate
- ClinicalTrials.gov/NCT01134809
- Full Text Sources
- Other Literature Sources
- Medical
![Fig. 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7957361/bin/gr2.jpg)
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Source: PubMed