Vo₂ kinetics associated with moderate-intensity exercise in heart failure: Impact of intrathecal fentanyl inhibition of group III/IV locomotor muscle afferents

Heart failure (HF) patients demonstrate impaired pulmonary, circulatory, and nervous system responses to exercise. While HF demonstrates prolonged [time constant (τ)] pulmonary O₂ uptake Vo₂ on-kinetics, contributing to exercise intolerance, it is unknown whether abnormal Vo₂ kinetics couple with ventilatory and circulatory dysfunction secondary to impaired group III/IV afferents in HF. Because lower lumbar intrathecal fentanyl inhibits locomotor muscle afferents, resulting in improved exercise ventilation and hemodynamics, we tested these hypotheses: HF will demonstrate 1) rapid Vo₂ on-kinetics and 2) attenuated steady-state Vo₂ amplitude and O₂ deficit (O₂def) during exercise with fentanyl versus placebo. On separate visits (randomized), breath-by-breath Vo₂ was measured in HF (ejection fraction: 27 ± 6%, New York Heart Association class I–III) and age- and sex-matched controls (both n = 9, ages: 60 ± 6 vs. 63 ± 8 yr, P = 0.37) during cycling transitions at 65% peak workload (78 ± 24 vs. 115 ± 39 W, P < 0.01) with intrathecal fentanyl or placebo. Regardless of group or condition, optimal phase II (primary component) curve fits reflected a phase I period equal to 35 s (limb-to-lung timing) via single-exponential functions. Condition did not affect steady-state Vo₂, the phase II τ of Vo₂, or O₂def within controls (P > 0.05). Without differences in steady-state Vo₂, reduced O₂def in fentanyl versus placebo within HF (13 ± 4 vs. 22 ± 15 ml/W, P = 0.04) was accounted for by a rapid phase II τ of Vo₂ in fentanyl versus placebo within HF (45 ± 11 vs. 57 ± 14 s, P = 0.04), respectively. In an integrative manner, these data demonstrate important effects of abnormal locomotor muscle afferents coupled to pulmonary and circulatory dysfunction in determining impaired exercise Vo₂ in HF. Effects of abnormal muscle afferents on impaired exercise Vo₂ and hence exercise intolerance may not be discernable by independently assessing steady-state Vo₂ in HF. NEW & NOTEWORTHY Inhibition of locomotor muscle afferents results in rapid primary-component O₂ uptake Vo₂ onkinetics accounting for the decreased O₂ deficit in heart failure (HF). This study revealed that abnormal musculoskeletal–neural afferents couple with pulmonary and circulatory dysfunction to provoke impaired exercise Vo₂ in HF. Steady-state Vo₂ cannot properly phenotype abnormal muscle afferent contributions to impaired exercise Vo₂ in HF.