Improved Ventilatory Efficiency with Locomotor Muscle Afferent Inhibition is Strongly Associated with Leg Composition in Heart Failure

Manda L. Keller-Ross, Bruce D. Johnson, Rickey E. Carter, Michael J. Joyner, John H. Eisenach, Timothy B. Curry, Thomas P. Olson

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Background: Skeletal muscle atrophy contributes to increased afferent feedback (group III and IV) and may influence ventilatory control (high VE/VCO2 slope) in heart failure (HF). Objective This study examined the influence of muscle mass on the change in VE/VCO2 with afferent neural block during exercise in HF. Methods: 17 participants [9 HF (60 ± 6 yrs) and 8 controls (CTL) (63 ± 7 yrs, mean ± SD)] completed 3 sessions. Session 1: dual energy x-ray absorptiometry and graded cycle exercise to volitional fatigue. Sessions 2 and 3: 5 min of constant-work cycle exercise (65% of peak power) randomized to lumbar intrathecal injection of fentanyl (afferent blockade) or placebo. Ventilation (VE) and gas exchange (oxygen consumption, VO2; carbon dioxide production, VCO2) were measured. Results: Peak work and VO2 were lower in HF (p < 0.05). Leg fat was greater in HF (34.4 ± 3.0 and 26.3 ± 1.8%) and leg muscle mass was lower in HF (63.0 ± 2.8 and 70.4 ± 1.8%, respectively, p < 0.05). VE/VCO2 slope was reduced in HF during afferent blockade compared with CTL (- 18.8 ± 2.7 and - 1.4 ± 2.0%, respectively, p = 0.02) and was positively associated with leg muscle mass (r2 = 0.58, p < 0.01) and negatively associated with leg fat mass (r2 = 0.73, p < 0.01) in HF only. Conclusions: HF patients with the highest fat mass and the least leg muscle mass had the greatest improvement in VE/VCO2 with afferent blockade with leg fat mass being the only predictor for the improvement in VE/VCO2 slope. Both leg muscle mass and fat mass are important contributors to ventilatory abnormalities and strongly associated to improvements in VE/VCO2 slope with locomotor afferent inhibition in HF.

Original languageEnglish (US)
Pages (from-to)159-166
Number of pages8
JournalInternational Journal of Cardiology
StatePublished - Jan 1 2016

Bibliographical note

Funding Information:
Acknowledgment of Grant Support: This work was supported by: American Heart Association (AHA) grant 12GRNT1160027 (TPO) , National Center for Advancing Translational Science (NCATS) grant KL2TR000136 (TPO) , NIH grants HL71478 (BDJ) , HL46493 (MJJ), the Frank R. Shari Caywood Professorship (MJJ). MLKR is supported by a NIH/NIAMS T32AR56950 grant.

Publisher Copyright:
© 2015 Elsevier Ireland Ltd.


  • Group III/IV
  • exercise
  • fentanyl
  • ventilation


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