title: Chemical mediators of the muscle ergoreflex in chronic heart failure: a putative role for prostaglandins in reflex ventilatory control.
abstract: BACKGROUND
  The overactivity of ergoreceptors (intramuscular afferents sensitive to products of skeletal muscle work) may be responsible for the abnormal responses to exercise and symptoms of exercise intolerance in chronic heart failure (CHF); however, little is known of the chemical nature of the stimuli involved. We investigated biochemical factors (H+, VCO2, VO2, HCO3, K+, phosphate, lactate, PGE2, PGF(1alpha), and bradykinin) potentially involved in ergoreceptor activation.
  
  
  RESULTS
  Sixteen stable patients with CHF (64.9+/-2.7 years, peak VO2 15.8+/-0.7 mL/kg per min) and 10 age-matched controls were studied. The ergoreceptor test involved two 5-minute handgrip exercises. On one occasion, the subjects recovered normally (control recovery), whereas on the other a posthandgrip regional circulatory occlusion was induced in the exercising arm, isolating the stimulation of the ergoreceptor after exercise. The ergoreflex was quantified as the difference in ventilation between the posthandgrip regional circulatory occlusion and the control recovery periods. During the protocol, the local muscular blood effluent concentrations of metabolic mediators were assessed. Patients had an ergoreflex effect on ventilation greater than controls (4.8+/-1.4 versus 0.4+/-0.1 L/min, P<0.01). During the ergoreflex test in patients, the following metabolites were elevated with respect to resting values in comparison with controls: PGE2 (3.7+/-0.7 versus 1.1+/-0.2 pg/mL), PGF(1alpha) (16.2+/-2.8 versus 7.2+/-1.2 pg/mL), and bradykinin (2.1+/-0.3 versus 1.0+/-0.1 pg/mL), P<0.05 for all comparisons. Only the increases in prostaglandins were predictors of the ergoreflex response (r>0.41, P<0.01).
  
  
  CONCLUSIONS
  Although multiple metabolites are concentrated in exercising muscle in CHF, only prostaglandins correlated with ergoreflex activity, suggesting these factors as potential triggers to the exaggerated ergoreflex, which is characteristic of CHF. This may have important implications for novel therapies to improve exercise tolerance.
authors.affiliation: National Heart & Lung Institute, and Royal Brompton Hospital, Imperial College School of Science, Technology and Medicine, London, UK.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Scott
authors.forename: Roland
authors.initials: R
authors.lastname: Wensel
authors.forename: Constantinos H
authors.initials: CH
authors.lastname: Davos
authors.forename: Michael
authors.initials: M
authors.lastname: Kemp
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kaczmarek
authors.forename: James
authors.initials: J
authors.lastname: Hooper
authors.forename: Andrew J S
authors.initials: AJ
authors.lastname: Coats
authors.forename: Massimo F
authors.initials: MF
authors.lastname: Piepoli
mesh_terms: D000368:Aged; D001241:Aspirin / Q000494:pharmacology; D001920:Bradykinin / Q000097:blood; D002628:Chemoreceptor Cells / Q000378:metabolism; D002908:Chronic Disease; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015444:Exercise; D005080:Exercise Test; D005260:Female; D006225:Hand; D006333:Heart Failure / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D006801:Humans; D007700:Kinetics; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply / Q000503:physiopathology*; D017202:Myocardial Ischemia / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology; D011453:Prostaglandins / Q000097:blood / Q000502:physiology*; D011522:Protons; D012123:Pulmonary Ventilation; D012018:Reflex / Q000502:physiology*
chemical_list: D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011522:Protons; D019344:Lactic Acid; D001241:Aspirin; D001920:Bradykinin