title: Influence of locomotor muscle afferent inhibition on the ventilatory response to exercise in heart failure.
abstract: What is the central question of this study? Patients with heart failure often develop ventilatory abnormalities at rest and during exercise, but the mechanisms underlying these abnormalities remain unclear. This study investigated the influence of inhibiting afferent neural feedback from locomotor muscles on the ventilatory response during exercise in heart failure patients. What is the main finding and its importance? Our results suggest that inhibiting afferent feedback from locomotor muscle via intrathecal opioid administration significantly reduces the ventilatory response to exercise in heart failure patients. Patients with heart failure (HF) develop ventilatory abnormalities at rest and during exercise, but the mechanism(s) underlying these abnormalities remain unclear. We examined whether the inhibition of afferent neural feedback from locomotor muscles during exercise reduces exercise ventilation in HF patients. In a randomized, placebo-controlled design, nine HF patients (age, 60 ± 2 years; ejection fraction, 27 ± 2%; New York Heart Association class 2 ± 1) and nine control subjects (age, 63 ± 2 years) underwent constant-work submaximal cycling (65% peak power) with intrathecal fentanyl (impairing the cephalad projection of opioid receptor-sensitive afferents) or sham injection. The hypercapnic ventilatory response was measured to determine whether cephalad migration of fentanyl occurred. There were no differences in hypercapnic ventilatory response within or between groups in either condition. Despite a lack of change in ventilation, tidal volume or respiratory rate, HF patients had a mild increase in arterial carbon dioxide (P(aCO(2)) and a decrease in oxygen (P(aO(2)); P < 0.05 for both) at rest. The control subjects demonstrated no change in P(aCO(2)), P(aO(2)), ventilation, tidal volume or respiratory rate at rest. In response to fentanyl during exercise, HF patients had a reduction in ventilation (63 ± 6 versus 44 ± 3 l min(-1), P < 0.05) due to a lower respiratory rate (30 ± 1 versus 26 ± 2 breaths min(-1), P < 0.05). The reduced ventilation resulted in lower P aO 2 (97.6 ± 2.5 versus 79.5 ± 3.0 mmHg, P < 0.05) and increased P(aCO(2)) (37.3 ± 0.9 versus 43.5 ± 1.1 mmHg, P < 0.05), with significant improvement in ventilatory efficiency (reduction in the ventilatory equivalent for carbon dioxide; P < 0.05 for all). The control subjects had no change in ventilation or measures of arterial blood gases. These data suggest that inhibition of afferent feedback from locomotor muscle significantly reduces the ventilatory response to exercise in HF patients.
authors.affiliation: * Mayo Clinic, Division of Cardiovascular Diseases, 200 First Street SW, Rochester, MN 55905, USA. olson.thomas2@mayo.edu.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Olson
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Joyner
authors.forename: John H
authors.initials: JH
authors.lastname: Eisenach
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Curry
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Johnson
mesh_terms: D002245:Carbon Dioxide / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005260:Female; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009132:Muscles / Q000294:innervation* / Q000378:metabolism / Q000502:physiology*; D009475:Neurons, Afferent / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology; D011659:Pulmonary Gas Exchange / Q000502:physiology; D012123:Pulmonary Ventilation / Q000502:physiology*; D012119:Respiration; D056152:Respiratory Rate / Q000502:physiology; D012146:Rest / Q000502:physiology; D013990:Tidal Volume / Q000502:physiology
chemical_list: D002245:Carbon Dioxide; D010100:Oxygen