Inspiratory and leg muscle blood flows during inspiratory muscle metaboreflex activation in heart failure with preserved ejection fraction

Shane M. Hammer, Eric J. Bruhn, Thomas G. Bissen, Jessica D. Muer, Nicolas Villarraga, Barry A. Borlaug, Thomas P. Olson, Joshua R. Smith

Research output: Contribution to journalArticlepeer-review


The purpose of this study was to determine the cardiovascular consequences elicited by activation of the inspiratory muscle metaboreflex in patients with heart failure with preserved ejection fraction (HFpEF) and controls. Patients with HFpEF (n = 15; 69 ± 10 yr; 33 ± 4 kg/m2) and controls (n = 14; 70 ± 8 yr; 28 ± 4 kg/m2) performed an inspiratory loading trial at 60% maximal inspiratory pressure (PIMAX) until task failure. Mean arterial pressure (MAP) was measured continuously. Near-infrared spectroscopy and bolus injections of indocyanine green dye were used to determine the percent change in blood flow index (%ΔBFI) from baseline to the final minute of inspiratory loading in the vastus lateralis and sternocleidomastoid muscles. Vascular resistance index (VRI) was calculated. Time to task failure was shorter in HFpEF than in controls (339 ± 197 s vs. 626 ± 403 s; P = 0.02). Compared with controls, patients with HFpEF had a greater increase from baseline in MAP (16 ± 7 vs. 10 ± 6 mmHg) and vastus lateralis VRI (76 ± 45 vs. 32 ± 19%) as well as a greater decrease in vastus lateralis %ΔBFI (-32 ± 14 vs. -17 ± 9%) (all, P < 0.05). Sternocleidomastoid %ΔBFI normalized to absolute inspiratory pressure was higher in HFpEF compared with controls (8.0± 5.0 vs. 4.0± 1.9% per cmH2O·s; P = 0.03). These data indicate that patients with HFpEF exhibit exaggerated cardiovascular responses with inspiratory muscle metaboreflex activation compared with controls. NEW & NOTEWORTHY Respiratory muscle dysfunction is thought to contribute to exercise intolerance in heart failure with preserved ejection fraction (HFpEF); however, the underlying mechanisms are unknown. In the present study, patients with HFpEF had greater increases in leg muscle vascular resistance index and greater decreases in leg muscle blood flow index compared with controls during inspiratory resistive breathing (to activate the metaboreflex). Furthermore, respiratory muscle blood flow index responses normalized to pressure generation during inspiratory resistive breathing were exaggerated in HFpEF compared with controls.

Original languageEnglish (US)
Pages (from-to)1202-1211
Number of pages10
JournalJournal of applied physiology
Issue number5
StatePublished - Nov 2022


  • HFpEF
  • inspiratory muscle weakness
  • respiratory muscle metaboreflex

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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