Introduction: Exercise intolerance is a hallmark feature of human heart failure (HF); however, the underlying mechanisms and subsequent treatment strategies remain unresolved. We have previously demonstrated in HF that inhibition of locomotor muscle Aδ and C afferents via lower lumbar intrathecal injection of fentanyl during fixed-load submaximal exercise leads to improved ventilatory efficiency and rapid on-transient oxygen uptake (VO2) kinetics without affecting VO2amplitude. This suggests impaired central hemodynamics cannot independently explain exercise intolerance in HF; but, that mechanisms influential to the O2 transport chain at the periphery plays an important role. Incremental cardiopulmonary exercise testing (CPET) is an important prognostic tool in HF and therefore it is important to define the impact of locomotor muscle afferents on exercise capacity during CPET in HF.
Hypothesis: Lower lumbar intrathecal fentanyl injection prior to CPET will lead to increased peak exercise workload without effects on cardiac index (QI) and VO2 in HF.
Methods: In a randomized, placebo controlled cross-over design, 7 HF (LVEF%=35±11; N=3/4, NYHA class I/II) and 7 age matched healthy controls (CTL) (age=60±8 vs 60±7 yrs; and BSA=2.1±0.2 vs 2.0±0.2 m2; both P>0.05) completed incremental cycling CPET with lumbar intrathecal fentanyl (FNL) or sham. Breath-by-breath gas exchange was measured continuously via open circuit metabolic system. QI was measured via open circuit acetylene washin.
Results: There was no effect of FNT on VO2 or QI at rest (P>0.05). Peak exercise watts (W) increased with FNT vs sham in HF (125±35 vs 109±33 W) and CTL (160±41 vs 140±40 W). Peak VO2 and QI were similar in FNT and sham in HF (22±5 vs 19±4 mL/kg/min; 7.1±1.7 vs 6.6±1.5 L/min/m2, respectively) and CTL (29±8 vs 25±8 mL/kg/min; 8.8±2.9 vs 7.7±0.9 L/min/m2, respectively) (all P>0.05).
Conclusions: Despite no significant increase in peak VO2 or QI with FNT, HF demonstrated increased peak W, suggesting improved exercise capacity. While preliminary in nature, these data suggest abnormal locomotor muscle Aδ and C afferents synergize with mechanisms influential to the O2 transport chain at the skeletal muscle level to play a major role in exercise intolerance in HF.