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Energy production in patients with chronic obstructive pulmonary disease: Evidence of mitochondrial and not O 2 supply limitation
Author(s) -
Layec Gwenael,
Hart Corey,
Trinity Joel,
Haseler Luke,
Le Fur Yann,
Jeong EunKee,
Richardson Russell
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1245.13
Subject(s) - hyperaemia , medicine , copd , perfusion , cardiology , blood flow , mitochondrion , endocrinology , ischemia , chemistry , biochemistry
It is well documented that chronic obstructive pulmonary disease (COPD) is associated with both muscular and vascular dysfunctions. Interestingly, although both peripheral oxygen (O 2 ) transport and muscle O 2 utilization capacity appear to be impaired in patients with COPD, it is still unclear which peripheral component of the O 2 cascade actually limits overall muscle aerobic capacity. Therefore, purpose of the present study was to determine whether mitochondrial function in vivo is limited by convective O 2 delivery or the intrinsic capacity of mitochondria to synthesize ATP in patients with COPD. To this aim, we combined phosphorus magnetic resonance spectroscopy ( 31 P‐MRS), near‐infrared spectroscopy (NIRS), and Doppler ultrasound, to examine the effect of superimposing reactive hyperaemia (RH), induced by a period of brief ischemia during the last min of exercise, on O 2 delivery and mitochondrial function in the calf muscle of 16 patients with moderate to severe COPD in comparison to free‐flow conditions (FF). Limb blood flow [area under the curve (AUC), FF: 2.5 ± 1.2 L; RH: 3.3 ± 1.0 L, P <0.05] and convective O 2 delivery (AUC, FF: 0.46 ± 0.23 L; RH: 0.61 ± 0.21 L, P =0.08) were increased in RH in comparison to FF. RH was also associated with significantly higher capillary blood flow (AUC, FF: 26 ± 14 L; RH: 37 ± 25 L, P <0.05). However, despite an increased muscle perfusion and O 2 delivery, the peak rate of mitochondrial ATP synthesis did not differ significantly between conditions (FF: 28 ± 14 mM.min −1 ; RH: 27 ± 9 mM.min −1 , P =0.83). Taken together, these results indicate that an increase in convective O 2 delivery does not improve mitochondrial function in the plantar flexor muscles of the patients with COPD, thereby revealing that the peak rate of mitochondrial ATP synthesis of these patients appears to be limited by the intrinsic mitochondrial capacity and not O 2 availability. Support or Funding Information This work was funded in part by grants from the Flight Attendant Medical Research Institute (FAMRI), NIH National Heart, Lung, and Blood Institute (K99HL125756, PO1 HL 091830) and VA Merit grant E6910R.