1. Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function
- Author
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Krishna K. Varadhan, Dileep N. Lobo, Paul L. Greenhaff, Dumitru Constantin-Teodosiu, Despina Constantin, and Ryan P. Atkins
- Subjects
Male ,0301 basic medicine ,Biopsy ,Mitochondrial pyruvate dehydrogenase complex ,Critical Care and Intensive Care Medicine ,Adenosine Triphosphate ,0302 clinical medicine ,Lower limb muscle ,Abdomen ,Medicine ,Postoperative Period ,Nutrition and Dietetics ,TNF-α, tumour necrosis factor alpha ,Muscle inflammatory responses ,Pyruvate dehydrogenase complex activity ,Middle Aged ,Pyruvate dehydrogenase complex ,FOXO1, Forkhead box transcription factor 1 ,Lower Extremity ,Anesthesia ,PDC, pyruvate dehydrogenase complex ,Original Article ,Female ,medicine.symptom ,ATP, adenosine triphosphate ,ETC, electron transport chain ,TCA, tricarboxylic acid ,Abdominal surgery ,MAPR, maximal mitochondrial ATP production rates ,Pyruvate Dehydrogenase Complex ,030209 endocrinology & metabolism ,Inflammation ,PDK4, pyruvate dehydrogenase kinase isoform 4 ,Muscle mitochondrial activity ,MAFbx, muscle atrophy F-box protein ,Anesthesia Procedure ,03 medical and health sciences ,NADH, nicotinamide adenine dinucleotide ,Humans ,Muscle, Skeletal ,030109 nutrition & dietetics ,business.industry ,Metabolic response ,ADP, adenosine diphosphate ,IL, interleukin ,Mitochondria, Muscle ,Clinical trial ,VL, vastus lateralis ,business - Abstract
© 2020 The Author(s) 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).
- Published
- 2021