Influence of locomotor muscle group III/IV afferents on cardiovascular and ventilatory responses in human heart failure during submaximal exercise

Joshua R. Smith, Michael J. Joyner, Timothy B. Curry, Barry A. Borlaug, Manda L. Keller-Ross, Erik H. Van Iterson, Thomas P. Olson

Research output: Contribution to journalArticlepeer-review


The purpose of this study is to determine the influence of locomotor muscle group III/IV afferent inhibition on central and peripheral hemodynamics at multiple levels of submaximal cycling exercise in patients with heart failure with reduced ejection fraction (HFrEF). Eleven patients with HFrEF and nine healthy matched controls were recruited. The participants performed a multiple stage [i.e., 30 W, 50%peak workload (WL), and a workload eliciting a respiratory exchange ratio (RER) of ~1.0] exercise test with lumbar intrathecal fentanyl (FENT) or placebo (PLA). Cardiac output (Q˙ TOT) was measured via open-circuit acetylene wash-in technique and stroke volume was calculated. Leg blood flow (Q˙ L) was measured via constant infusion thermodilution and leg vascular conductance (LVC) was calculated. Radial artery and femoral venous blood gases were measured. For HFrEF, stroke volume was higher at the 30 W (FENT: 110 ± 21 vs. PLA: 100 ± 18 mL), 50%peak WL (FENT: 113 ± 22 vs. PLA: 103 ± 23 mL), and RER = 1.0 (FENT: 119 ± 28 vs. PLA: 110 ± 26 mL) stages, whereas heart rate and systemic vascular resistance were lower with fentanyl than with placebo (all, P < 0.05). Q˙ TOT in HFrEF and Q˙ TOT, stroke volume, and heart rate in controls were not different between fentanyl and placebo (all, P > 0.19). During submaximal exercise, controls and patients with HFrEF exhibited increased leg vascular conductance (LVC) with fentanyl compared with placebo (all, P < 0.04), whereas no differences were present in Q˙ L or O2 delivery with fentanyl (all, P > 0.20). Taken together, these findings provide support for locomotor muscle group III/IV afferents playing a role in integrative control mechanisms during submaximal cycling exercise in patients with HFrEF and older controls. NEW & NOTEWORTHY Patients with HFrEF exhibit severe exercise intolerance. One of the primary peripheral mechanisms contributing to exercise intolerance in patients with HFrEF is locomotor muscle group III/IV afferent feedback. However, it is unknown whether these afferents impact the central and peripheral responses during submaximal cycling exercise. Herein, we demonstrate that inhibition of locomotor muscle group III/IV afferent feedback elicited increases in stroke volume during submaximal exercise in HFrEF, but not in healthy controls.

Original languageEnglish (US)
Pages (from-to)903-914
Number of pages12
JournalJournal of applied physiology
Issue number4
StatePublished - Apr 2022

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health under Grants HL126638 (to T. P. Olson), HL128526 (to B. A. Borlaug), HL139854 (to M. J. Joyner), T32AR56950 (to M. L. Keller-Ross), T32HL007111 (to J. R. Smith), K12 HD065987 (to J. R. Smith), and American Heart Association Grant 18POST3990251 (to J. R. Smith). This publication was also made possible through the support of the Mary Kathryn and Michael B. Panitch Career Development Award in Hypertension Research Honoring Gary Schwartz, M.D. (to J. R. Smith).

Publisher Copyright:
Copyright © 2022 the American Physiological Society.


  • blood pressure control
  • exercise pressor reflex
  • sympathetic nervous system activity
  • Stroke Volume
  • Heart Failure/drug therapy
  • Humans
  • Exercise/physiology
  • Muscle, Skeletal/physiology
  • Cardiovascular System

PubMed: MeSH publication types

  • Journal Article


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