V̇o 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 O uptake (V̇o) on-kinetics, contributing to exercise intolerance, it is unknown whether abnormal V̇o 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 ) rapid V̇o on-kinetics and ) attenuated steady-state V̇o amplitude and O deficit (Odef) during exercise with fentanyl versus placebo. On separate visits (randomized), breath-by-breath V̇o was measured in HF (ejection fraction: 27 ± 6%, New York Heart Association class I-III) and age- and sex-matched controls (both = 9, ages: 60 ± 6 vs. 63 ± 8 yr, = 0.37) during cycling transitions at 65% peak workload (78 ± 24 vs. 115 ± 39 W, < 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 V̇o, the phase II τ of V̇o, or Odef within controls ( > 0.05). Without differences in steady-state V̇o, reduced Odef in fentanyl versus placebo within HF (13 ± 4 vs. 22 ± 15 ml/W, = 0.04) was accounted for by a rapid phase II τ of V̇o in fentanyl versus placebo within HF (45 ± 11 vs. 57 ± 14 s, = 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 V̇o in HF. Effects of abnormal muscle afferents on impaired exercise V̇o and hence exercise intolerance may not be discernable by independently assessing steady-state V̇o in HF. Inhibition of locomotor muscle afferents results in rapid primary-component O uptake (V̇o) on-kinetics accounting for the decreased O deficit in heart failure (HF). This study revealed that abnormal musculoskeletal-neural afferents couple with pulmonary and circulatory dysfunction to provoke impaired exercise V̇o in HF. Steady-state V̇o cannot properly phenotype abnormal muscle afferent contributions to impaired exercise V̇o in HF.