Abstract
SummaryBackground & aimsThis 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.MethodsFifteen 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).ResultsMuscle 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.ConclusionsPDC 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 registrationRegistered at (NCT01134809).
Highlights
Skeletal muscle is the primary site for insulin-dependent glucose uptake, and surgical trauma appears to play an important role in the downregulation of muscle glucose uptake and oxidation following major abdominal surgery in patients [2] and animal models [3] that includes inhibition of mitochondrial pyruvate dehydrogenase complex (PDC) activation via upregulation of pyruvate dehydrogenase kinase 4 isoform (PDK4) [4]
This study aimed to assess the impact of major abdominal surgery on PDC activity and mitochondrial function in a large muscle group (VL) distant to the site of surgical trauma
We have previously demonstrated that inflammation-mediated impairment of PDC plays an important role in the acute dysregulation of muscle metabolism in an animal model of endotoxemia [5], and in patients within 6e8 h of admission to the intensive care unit [6]
Summary
Whole-body insulin resistance accompanies surgical trauma, and appears to be proportional to the magnitude of injury incurred [1]. Mitochondria isolated the second day following surgical trauma in pigs were reported to exhibit diminished ADP stimulated respiration for pyruvate [3], the relevance of this postsurgical response to the acute human surgical condition remains unclear 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. 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.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
