Document Detail


Chemical mediators of the muscle ergoreflex in chronic heart failure: a putative role for prostaglandins in reflex ventilatory control.
MedLine Citation:
PMID:  12105161     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. METHODS AND 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:
Adam C Scott; Roland Wensel; Constantinos H Davos; Michael Kemp; Agnieszka Kaczmarek; James Hooper; Andrew J S Coats; Massimo F Piepoli
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  106     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-07-09     Completed Date:  2002-07-19     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  214-20     Citation Subset:  AIM; IM    
Affiliation:
National Heart & Lung Institute, and Royal Brompton Hospital, Imperial College School of Science, Technology and Medicine, London, UK.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aspirin / pharmacology
Bradykinin / blood
Chemoreceptor Cells / metabolism
Chronic Disease
Cyclooxygenase Inhibitors / pharmacology
Exercise*
Exercise Test
Female
Hand
Heart Failure / blood,  diagnosis,  physiopathology*
Humans
Kinetics
Lactic Acid / blood
Male
Middle Aged
Muscle, Skeletal / blood supply,  physiopathology*
Myocardial Ischemia / blood,  diagnosis,  physiopathology
Prostaglandins / blood,  physiology*
Protons
Pulmonary Ventilation
Reflex / physiology*
Chemical
Reg. No./Substance:
0/Cyclooxygenase Inhibitors; 0/Prostaglandins; 0/Protons; 50-21-5/Lactic Acid; 50-78-2/Aspirin; 58-82-2/Bradykinin

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