Krajcova 2018 ICO134

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Skeletal muscle bioenergetics in critically ill patients: effect of early rehabilitation on mitochondrial functions and insulin resistance during and 6 months after critical illness.

Link: Mitochondr Physiol Network 23.08

Krajcova A, Urban T, Waldauf P, Blahutova B, Gojda J, Duska F (2018)

Event: IOC134

The hallmark of metabolic changes in skeletal muscle during critical illness is impaired aerobic phosphorylation in mitochondria [1] and reduced insulin-stimulated glucose disposal [2]. We asked whether these parameters can be influenced by very early (started <48 hours) rehabilitation using functional-electrical stimulation assisted supine cycling (FESCE).

In tested subgroup of patients in a prospective randomized clinical trial of early rehabilitation (NCT 02864745) we performed serial vastus lateralis muscle biopsies and euglycemic hyperinsulinaemic (120 mIU.m-2 BSA.min-1) clamps at days 0, 7 and 180. Mitochondrial functions were assessed by high resolution respirometry (Oroboros O2k) using native skeletal muscle homogenates, as previously described [3], with a cohort (n=8) of metabolically healthy patients undergoing hip replacement surgery as the control group. Electron flux through mitochondrial respiratory complexes was measured by addition of specific substrates and inhibitors [3].

In the control group, the mean rehabilitation dose was 22 min a day, whilst interventional group was receiving 77 min/day (p<0.01). Insulin resistance: Glucose disposal was lowest in the acute phase of critical illness (1.53±0.99 vs. 1.21±0.92 mmol/min) and improved a little after 7 days in both groups (to 2.23±1.01 vs. 2.05±0.82 mmol/min) and after 6 months (3.32±0.59 vs. 2.72±0.90 mmol/min). Bioenergetic functions: Critical illness led to a mild impairment of aerobic phosphorylation, with major defect being in respiratory complex I and II, whilst fatty acid oxidation was upregulated (see Table 1). In a standard rehabilitation group, this pattern persisted up until 6 months after the critical illness, whilst in the early rehabilitation group it seems to normalize or even achieve the supra-normal values. The major limitation indeed is the low number of subjects accumulated so far in this ongoing study. This is the reason why these data are to be considered preliminary and have not been formally statistically processed.

In conclusion, our preliminary data show that critical illness leads to profound changes in skeletal muscle bioenergetics, which seem to persist in survivors at least 6 months, but could be influenced by early rehabilitation.


Bioblast editor: Plangger M O2k-Network Lab: CZ Prague Krajcova A


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, Patients  Pathology: Other 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Homogenate  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 


Affiliations and Support

OXYLAB – Lab Mitochondrial Physiology, Dept Anaesthesia Intensive Care, Third Fac Medicine, Charles Univ and FNKV Univ Hospital, Prague, Czech Republic. - adela.krajcova@lf3.cuni.cz

The work was supported by PROGRES Q37, AZV 16-28663 A.

Tables

Table 1: Mitochondrial functional indices expressed as % of values in the control group. Note: ATP = aerobic phosphorylation; FAO = fatty acid oxidation

n Day ATP Complex I Complex II Complex III Complex IV FAO
Intervention 13 1 94 72 77 122 84 115
9 7 104 84 90 118 99 132
3 180 141 100 137 181 136 163
Standard 11 1 92 76 74 105 80 117
8 7 99 75 76 114 86 104
3 180 100 62 81 114 82 106


References

  1. Jiroutková K, Krajčová A, Ziak J, Fric M, Waldauf P, Džupa V, Gojda J, Němcova-Fürstová V, Kovář J, Elkalaf M, Trnka J, Duška F (2015) Mitochondrial function in skeletal muscle of patients with protracted critical illness and ICU-acquired weakness. Crit Care 19:448.
  2. Bakalar B, Duska F, Pachl J, Fric M, Otahal M, Pazout J, Andel M (2006) Parenterally administered dipeptide alanyl-glutamine prevents worsening of insulin sensitivity in multiple-trauma patients. Crit Care Med 34:381-6.
  3. Ziak J, Krajcova A, Jiroutkova K, Nemcova V, Dzupa V, Duska F (2015) Assessing the function of mitochondria in cytosolic context in human skeletal muscle: adopting high-resolution respirometry to homogenate of needle biopsy tissue samples. Mitochondrion 21:106-12.