Intrathecal fentanyl blockade of afferent neural feedback from skeletal muscle during exercise in heart failure patients: Influence on circulatory power and pulmonary vascular capacitance

Background Secondary pulmonary hypertension is common in heart failure (HF) patients. We hypothesized that inhibition of feedback from locomotor muscle group III/IV neurons contributes to reduced pulmonary vascular pressures independent of changes in cardiac function during exercise in HF. Methods 9 HF patients (ages, 60 ± 2; EF, 26.7 ± 1.9%; New York Heart Association classes, I-III) and 9 age/gender matched controls (ages, 63 ± 2) completed five-minutes of constant-load cycling (65% Workload_peak) with intrathecal fentanyl or placebo on randomized separate days. Mean arterial pressure (MAP), heart rate (HR), end-tidal partial pressure of CO₂ (P_ETCO₂), and oxygen consumption (VO₂) were measured at rest and exercise. Non-invasive surrogates for cardiac power (circulatory power, CircP = VO₂ × MAP), stroke volume (oxygen pulse, O₂pulse = VO₂/HR), and pulmonary arterial pressure (GX_CAP = O₂pulse × P_ETCO₂) were calculated. Results At rest and end-exercise, differences between fentanyl versus placebo were not significant for CircP in HF or controls. Differences between fentanyl versus placebo for GX_CAP were not significant at rest in HF or controls. At end-exercise, GX_CAP was significantly higher with fentanyl versus placebo in HF (691 ± 59 versus 549 ± 38 mL/beat × mm Hg), but not controls (536 ± 59 versus 474 ± 43 mL/beat × mm Hg). Slopes (rest to end-exercise) for GX_CAP were significantly higher with fentanyl versus placebo in HF (95.1 ± 9.8 versus 71.6 ± 6.0 mL/beat × mm Hg), but not controls (74.3 ± 9.5 versus 60.8 ± 6.5 mL/beat × mm Hg). CircP slopes did not differ between fentanyl versus placebo in HF or controls (p > 0.05). Conclusion We conclude that feedback from locomotor muscle group III/IV neurons may evoke increases in pulmonary vascular pressures independent of changes in cardiac function during exercise in HF.