Abstract 16260: On-transient Vo2 Kinetics During Submaximal Exercise Are Influenced by Intrathecal Fentanyl Inhibition of Group III/IV Locomotor Afferents in Heart Failure Patients
Introduction: Peak oxygen uptake (VO2) is the gold standard measure of exercise tolerance in heart failure (HF). The pathophysiology of low peak VO2 in HF is incompletely understood. Thus, physiologic studies of VO2 responses during exercise are central to an improved mechanistic understanding of exercise intolerance in HF. We previously demonstrated inhibition of group III/IV locomotor afferents via intrathecal fentanyl blunts ventilation and blood pressure during submaximal exercise in HF. We hypothesized that locomotor muscle group III/IV afferent inhibition would improve on-transient VO2 kinetics during submaximal exercise in HF.
Methods: HF patients (N = 9; age, 60 ± 2; EF, 27 ± 2 %; NYHA class, I-III) and 9 age/gender matched controls (CTL; ages, 63 ± 2) completed 3 sessions of 5 min of fixed load cycling (65% PeakWORK) with intrathecal fentanyl (FEN) or placebo (PLB), on separate days (randomized). Breath-by-breath VO2 was measured via metabolic measurement system integrated with gas mass spectrometry. Data were interpolated to 1 s intervals and averaged across FNT or PLB sessions to model phase II (fast) time constants (τ2, 63% VO2) minus the cardiodynamic period (phase I) using a double exponential fit: VO2REST + A2[1 – e-(t-TD2)/τ2] + A3[1 – e-(t-TD3)/τ3]; where A2 = VO2 increase from rest (VO2REST) to end of Phase II; TD2 = Phase II time delay. Phase II mean response time (MRT) was calculated as: MRT = TD2 + τ2.
Results: Fixed workload was lower in HF vs CTL (78 ± 23 vs 121 ± 34 Watts, P=0.01). VO2REST did not differ between or within groups (P>0.05). In HF, A2 did not differ for FEN vs PLB (0.9 ± 0.1 vs 0.9 ± 0.1 L/min, P=0.35), but was lower with FEN in CTL (0.9 ± 0.2 vs 1.0 ± 0.2 L/min, P=0.03). TD2 was lower with FEN vs PLB for both HF (4 ± 4 vs 12 ± 4 s) and CTL (3 ± 6 vs 13 ± 2 s) (both P<0.03). HF (35 ± 12 vs 40 ± 14 s, P=0.06) and CTL (30 ± 5 vs 39 ± 6 s, P<0.01) had lower τ2 with FEN vs PLB, which was matched by MRT (39 ± 14 vs 52 ± 14 s, P=0.04; and 30 ± 13 vs 52 ± 7 s, P<0.01). There were no between group differences for A2, TD2, τ2, or MRT (P>0.05).
Conclusion: These data suggest inhibition of group III/IV muscle afferents speeds up VO2 on-kinetics in HF. Faster VO2 on-kinetics may be linked to higher exercise capacity which may have important implications in understanding the pathophysiology of HF.
- Cardiopulmonary exercise testing
- Oxygen uptake
- Physical activity and exercise
- Expired gas analysis
- Reflexes, cardiovascular
Author Disclosures: E.H. Van Iterson: None. B.D. Johnson: None. M.J. Joyner: None. T.B. Curry: None. T.P. Olson: None.
- © 2016 by American Heart Association, Inc.