Vo^sub 2^ kinetics associated with moderate-intensity exercise in heart failure: impact of intrathecal fentanyl inhibition of group III/IV locomotor muscle afferents

• Published in: American journal of physiology. Heart and circulatory physiology 2017-07, Vol.313 (1), p.H114
• Main Authors: Van Iterson, Erik H, Johnson, Bruce D, Joyner, Michael J, Curry, Timothy B, Olson, Thomas P
• Format: Article
• Language: English
• Subjects: Anesthesia; Exercise; Exponential functions; Fentanyl; Heart failure; Hemodynamics; Impact analysis; Kinetics; Muscles; Muscular system; Nervous system; Steady state; Time constant; Ventilation; Workload
• ISSN: 0363-6135; 1522-1539

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.