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Stevens 2018 Br J Anaesth

From Bioblast
Stevens JL, McKenna H, Murray A, Jell G, Guliyeva M, Martin D (2018) Effects of major hepato-pancreatico-biliary surgery and general anaesthesia on skeletal-muscle mitochondrial respiration: a pilot study. Br J Anaesth.

Link: Open Access

Stevens JL, McKenna H, Murray A, Jell G, Guliyeva M, Martin D (2018)

Event: Br J Anaesth

In this pilot study, we sought to characterise changes in mitochondrial function during major hepato-pancreatico-biliary surgery under general anaesthesia (GA), and to determine if such changes are associated with preoperative measures of fitness.

Patients underwent cardiopulmonary exercise testing before surgery to obtain anaerobic threshold (AT) and peak oxygen uptake (VO2 peak). Skeletal-muscle biopsies were taken from the vastus lateralis under GA. High-resolution respirometry (O2k; Oroboros, Austria) of permeabilised muscle fibres was performed using a substrate-uncoupler-inhibitor titration protocol.[1,2]

Fourteen patients were recruited to the study. We observed a significant increase in mitochondrial oxygen consumption post-surgery in fatty acid oxidation and Complex I mediated states. We also found a significant reduction in mitochondrial coupling efficiency, electron transfer coupling efficiency (-0.03; P<0.04), and oxidative phosphorylation coupling efficiency (-0.03; P<0.02) after surgery compared with before surgery. Patients with an AT less than 11 ml kg-1 min-1 had a significantly lower mitochondrial coupling efficiency pre-surgery than those with an AT greater than 11 ml kg-1 min-1. There was also a correlation observed between mitochondrial coupling efficiency with VO2 peak (rยผ0.601; P<0.05). The relationships between AT, VO2 peak, and coupling efficiencies were no longer evident after surgery.

Our early findings show that the process of major hepato-pancreatico-biliary surgery under GA leads to an increase in mitochondrial oxygen consumption and reductions in mitochondrial coupling efficiencies.

Also, cycle ergometry findings correlated well with cell ergometry.


โ€ข Bioblast editor: Plangger M โ€ข O2k-Network Lab: UK London Martin DS


Labels: MiParea: Respiration 


Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized cells 

Regulation: Coupling efficiency;uncoupling 


HRR: Oxygraph-2k 


Affiliations

Stevens JL(1), McKenna H(1), Murray A(2), Jell G(1), Guliyeva M(1), Martin D(1)

  1. Div Surgery Interventional Sciences, Royal Free Hospital, Univ College London
  2. Univ Cambridge; UK

References

  1. Pesta D, Gnaiger E (2012) High-resolution respirometry: OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle. Methods Mol Biol 810:25-58.
  2. Horscroft JA, Kotwica AO, Laner V, West JA, Hennis PJ, Levett DZH, Howard DJ, Fernandez BO, Burgess SL, Ament Z, Gilbert-Kawai ET, Vercueil A, Landis BD, Mitchell K, Mythen MG, Branco C, Johnson RS, Feelisch M, Montgomery HE, Griffin JL, Grocott MPW, Gnaiger E, Martin DS, Murray AJ (2017) Metabolic basis to Sherpa altitude adaptation. Proc Natl Acad Sci U S A 114:6382-7.