title: Intrathecal fentanyl blockade of afferent neural feedback from skeletal muscle during exercise in heart failure patients: Influence on circulatory power and pulmonary vascular capacitance.
abstract: 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% Workloadpeak) with intrathecal fentanyl or placebo on randomized separate days. Mean arterial pressure (MAP), heart rate (HR), end-tidal partial pressure of CO2 (PETCO2), 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 (GXCAP=O2pulse × PETCO2) 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 GXCAP were not significant at rest in HF or controls. At end-exercise, GXCAP was significantly higher with fentanyl versus placebo in HF (691 ± 59 versus 549 ± 38 mL/beat × mmHg), but not controls (536 ± 59 versus 474 ± 43 mL/beat × mmHg). Slopes (rest to end-exercise) for GXCAP were significantly higher with fentanyl versus placebo in HF (95.1 ± 9.8 versus 71.6 ± 6.0 mL/beat × mmHg), but not controls (74.3 ± 9.5 versus 60.8 ± 6.5 mL/beat × mmHg). CircP slopes did not differ between fentanyl versus placebo in HF or controls (p>0.05).
  
  
  CONCLUSIONS
  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.
authors: Department of Kinesiology, University of Minnesota, Cooke Hall, 1900 University Ave. SE, Minneapolis, MN 55455, USA. Electronic address: vanit001@umn.edu.
authors: Erik H
authors: EH
authors: Van Iterson
authors: Department of Kinesiology, University of Minnesota, Cooke Hall, 1900 University Ave. SE, Minneapolis, MN 55455, USA.
authors: Eric M
authors: EM
authors: Snyder
authors: Division of Cardiovascular Diseases, Mayo Clinic, Gonda 5 South, 200 First Street, SW, Rochester, MN 55905, USA.
authors: Michael J
authors: MJ
authors: Joyner
authors: Division of Cardiovascular Diseases, Mayo Clinic, Gonda 5 South, 200 First Street, SW, Rochester, MN 55905, USA.
authors: Bruce D
authors: BD
authors: Johnson
authors: Division of Cardiovascular Diseases, Mayo Clinic, Gonda 5 South, 200 First Street, SW, Rochester, MN 55905, USA.
authors: Thomas P
authors: TP
authors: Olson
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004562:Electrocardiography; D015444:Exercise / Q000502:physiology*; D005260:Female; D005283:Fentanyl / Q000008:administration & dosage* / Q000009:adverse effects; D006333:Heart Failure / Q000503:physiopathology*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation*; D009475:Neurons, Afferent / Q000187:drug effects*; D016037:Single-Blind Method; D018924:Vascular Capacitance / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D005283:Fentanyl
keywords: Ergoreceptors; Fentanyl; Mechanoreceptor; Metaboreceptor; Pulmonary hypertension